GIFT   OF 
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A  TEXTBOOK 

OF 

ORGANIC  CHEMISTRY 


CHAMBERLAIN 


Aids  to  the  Mastery  of 

C  H  EMI STRY 


Ostwald's  Handbook  of  Colloid  Chemistry, 
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The  Theory,  Recognition  and  General  Physico- Chemi- 
cal Properties  of  Colloids.  By  DR.  WOLFGANG  OSTWALD, 
Leipzig;  translated  by  DR.  MARTIN  H.  FISCHER,  Univer- 
sity of  Cincinnati,  with  notes  by  EMIL  HATSCHEK,  Lon- 
don. Second  Edition  Revised,  63  Illustrations,  Reference 
Tables.  Octavo.  Cloth,  $4.50. 

McGuigan.     An  Introduction  to  Chemical 
Pharmacology 

Pharmacodynamics  in  Relation  to  Chemistry 
BY  HUGH  McGuiGAN,  PH.D.,  M.D.,  Professor  of  Phar- 
macology,  University  of  Illinois,    College  of   Medicine. 
Cloth,  $4.00. 

Autenreith.     The  Detection  of  Poisons  and 
Powerful  Drugs 

A  Laboratory  Guide.  Including  the  Quantitative 
Estimation  of  Medicinal  Principles  in  Certain  Crude 
Materials.  By  DR.  WILHELM  AUTENREITH,  Freiberg. 
Authorized  Translation  by  WILLIAM  H.  WARREN,  A.M., 
PH.D.,  (Harv.).  Fifth  Edition,  Revised,  Enlarged.  25 
Illustrations.  Cloth,  $3.50. 

Hackh.     Chemical  Reactions  and  Their 
Equations  -  . 

A  Guide  and  Reference  Book.  By  INGO  W.  D.  HACKH, 
PH.c.,  A.B.,  Professor  of  Biochemistry,  College  of  Physi- 
cians and  Surgeons,  San  Francisco.  8vo.  Cloth,  $1.75. 

Copaux-Leffmann.    Introduction  to  General 
Chemistry 

By  H.  COPAUX,  Professor  of  Inorganic  Chemistry  at 
the  School  of  Industrial  Chemistry  and  Physics  of  Paris, 
France.  Translated  by  HENRY  LEFFMANN,  M.D.  30 
Illustrations.  Cloth,  $2.00. 


P.  BLAKISTON'S  SON  &  CO. 

PUBLISHERS  -  PHILADELPHIA 


A   TEXTBOOK 

OF 

ORGANIC   CHEMISTRY 


BY 

JOSEPH  SCUDDER  CHAMBERLAIN,  PH.D. 

PROFESSOR  OF   ORGANIC  CHEMISTRY 
MASSACHUSETTS  AGRICULTURAL  COLLEGE 


PHILADELPHIA 

P.  BLAKISTON'S  SON  &  CO. 

1012  WALNUT  STREET 


VI  PREFACE 

already  studied  the  subject  may  find  it  of  value  for  its  general 
presentation.  In  its  method  and  order  of  treatment  the  book  is  the 
expression  of  the  author's  experience  during  the  last  ten  years  in 
teaching  the  subject  to  students,  most  of  whom  have  been  planning  to 
take  up  chemistry  as  a  profession. 

In  attempting  to  correlate  theoretical  principles  with  industrial 
practice  the  author  has  not  done  more  than  to  mention,  in  cases  where 
it  seems  desirable,  the  fact  that  a  given  synthesis  is  the  basis  of  indus- 
trial processes.  No  effort  has  been  made,  in  most  cases,  to  describe 
the  technical  procedure.  In  a  few  of  the  more  common  processes 
some  description  of  the  industrial  procedure  is  given,  but  without  any 
claim  that  it  is  exact  in  minute  detail.  It  is  important  to  emphasize 
the  fact,  that  oftentimes  in  industrial  practice,  reactions  while  no  doubt 
following  the  course  worked  out  in  the  laboratory,  are  nevertheless 
frequently  shortened  by  doubling  up  or  by  changing  physical  condi- 
tions, so  that  the  process  and  the  laboratory  synthesis  seem  to  be  quite 
distinct.  If  this  is  kept  in  mind  the  author  feels  that  the  student  will 
find  no  difficulty  in  gaining  from  a  study  of  this  text  that  fundamental 
knowledge  of  the  theory  of  organic  chemistry  on  which  all  practice 
rests,  and  at  the  same  time  a  realization  of  the  direct  connection  of 
this  theory  with  the  tremendous  industrial  application  of  organic 
chemistry  to  the  life  of  the  world. 

A  brief  discussion  of  the  separation,  purification,  identification, 
analysis  and  determination  of  molecular  weight  of  organic  com- 
pounds is  given  in  an  appendix  instead  of  in  an  introductory 
chapter 'as  is  customary.  In  the  presentation  of  the  above  topics, 
which  belong  more  especial)  y  to  a  laboratory  guide,  only  general 
methods  are  given  without  an^  of  the  details  that  must  be  observed 
in  each  case. 

The  author,  in  gathering  material  for  the  work,  has  had  access  to  all 
of  the  standard  books  on  the  subject,  and  to  a  limited  amount  of  orig- 
inal literature,  and  wishes  to  acknowledge  herewith  all  such  use  of 
texts  and  journal  articles.  No  references  to  literature  have  been  made 
except  where  direct  quotations  have  been  used,  as  in  the  author's 
opinion,  this  would  not  increase  the  value  of  the  book  as  a  text  for 
undergraduate  students.  A  list  of  books  used  for  reference  will' be 
found  at  the  end  of  the  volume,  and  to  these  in  particular  the  author 
acknowledges  his  indebtedness. 


PREFACE  Vll 

In  addition  he  wishes  to  acknowledge  the  assistance  and  coopera- 
tion of  friends  and  associates  who  have  read  and  criticized  the  manu- 
script, and  of  all  others  who  have  in  any  way  assisted  him  in  the  large 
task  which  he  has  attempted. 

JOSEPH  S.  CHAMBERLAIN. 
MASSACHUSETTS  AGRICULTURAL  COLLEGE, 
AMHERST,  MASSACHUSETTS. 


CONTENTS 

t 

PART  I 

A-CYCLIC  COMPOUNDS 
ALIPHATIC  SERIES 

PAGE 
INTRODUCTION  i 

A.  SIMPLER  SATURATED  COMPOUNDS  3 

I.  HYDROCARBONS  OF  THE  SATURATED  SERIES, 

PARAFFINS  3 

GENERAL  3 

Methane  4 

Marsh  gas, — .  Fire  damp, — .  Coal  gas, — .  .  Natural  gas, — .  Petroleum, — . 
Physical  properties, — .  Chemical  properties, — .  Formula, — .  Synthesis, — . 
Preparation, — .  Reactions, — .  Substitution, — .  Structure, — .  Tetra-valent 
carbon, — .  Saturated  compound, — .  Symmetrical  compound, — .  Constitu- 
tional formula, — .  Radical, — .  Methyl, — .  Methyl  halides, — . 

Ethane  15 

Synthesis, — .     Constitution, — . 

Propane,  Butane,  Pentane,  Hexane  and  Higher  Saturated  Hydrocarbons       18 

.  TABLE  I.  HOMOLOGOUS  SERIES  SATURATED  HYDROCARBONS    19 

Physical  properties, — .  Composition  and  constitution,- — .  Propane  and 
butane, — .  A-cyclic  or  open  chain  compounds, — .  Homologous  series, — . 
Names, — .  Alkyl, — .  Isomerism, — .  Structural  isomerism, — .  Isomeric  hy- 
drocarbons,— .  Butanes, — .  Synthesis, — .  Pentanes  and  hexanes, — .  Scheme 
of  relationships  methane  to  hexanes, — .  Normal  and  iso  compounds, — . 
Names/ — .  Systematic  nomenclature, — .  Official  nomenclature, — . 

TABLE  II.  NOMENCLATURE  OF  HYDROCARBONS       35 

Higher  hydrocarbons, — . 

ix 


Xll  CONTENTS 

PACE 

G.  MONO-HYDROXYL  SUBSTITUTION  PRODUCTS- 
ALCOHOLS  78 

GENERAL  78 

Alcohol  not  an  oxide, — .  Alcohol  and  sodium  reaction, — .  Alcohol  and 
phosphorus  trichloride  reaction, — .  Alcohol  and  hydrobromic  acid  reaction, — . 
Synthesis  of  alcohol  from  alkyl  halides, — .  Alcohol  of  crystallization, — . 
Water  type  compounds, — .  Hydroxyl  substitution  products, — .  Methyl 
alcohol, — .  Homologous  series  of  alcohols, — .  Names  of  alcohols, — . 

TABLE  IX.  NORMAL  PRIMARY  ALCOHOLS  SATURATED  SERIES        85 

TABLE  X.  ISOMERIC  ALCOHOLS  86 

Isomerism  of  alcohols, — .  Root  isomerism, — .  Position  isomerism, — .  Names 
of  isomeric  alcohols, — . 

Stereo -isomerism  88 

Optical  activity, — .  Dextro,  levo  and  inactive  compounds, — .  Pasteur, — . 
Theory  of  van't  Hoff-LeBel, — .  Asymmetric  carbon, — .  Stereo-isomerism, — . 
Tetrahedral  carbon, — .  Enantiomorphs, — .  Alcohols, — .  General  methods 
of  preparation, — .  General  properties  of  alcohols, — .  Natural  occurrence, — . 

Methyl  Alcohol— Methanol— Wood  Alcohol  94 

Manufacture  from  wood, — .  From  beet  sugar  residues, — .  Properties  and 
uses, — . 

Ethyl  Alcohol— Ethanofr— Grain  Alcohol  95 

Alcoholic  fermentation, — .  Yeast, — .  Catalytic  theory  of  Liebig, — .  Vital 
theory  of  Pasteur, — .  Enzyme  theory  of  Buchner, — .  Zymase, — .  Wine, — . 
Starch  and  diastase, — .  Absolute  alcohol, — .  Properties  and  uses  of 
alcohol, — . 

Alcoholic  Beverages  98 

Industrial  Alcohol  99 

Government  regulation  and  tax, — .     Proof  spirit, — .     Denatured  alcohol, — . 

TABLE  XL  ETHYL  ALCOHOL  (ptr  cent)  101 

Amyl  Alcohols— Pentanols— Fusel  Oil  101 

DERIVATIVES  OF  ALCOHOLS  102 

i.  ESTERS  OR  ETHEREAL  SALTS  102 

Alcohol  a  base  or  an  acid, — .     Esters  or  ethereal  salts, — .     Properties, — . 


CONTENTS  Xlll 

PAGE 
2.  ETHERS  105 

Synthesis, — .     Williamson's  synthesis, — . 

Simple  Ethers  and  Mixed  Ethers  106 

Names  of  ethers, — . 

TABLE  XII.  ETHERS  107 

Isomerism, — .     Class  isomerism, — .     Chemical  properties, — . 

Ethyl  Ether — Ethane -oxy-Ethane  108 

Commercial  manufacture, — .  Ether  the  anhydride  of  alcohol, — .  Properties 
of  ether, — . 

III.  OXIDATION  PRODUCTS  OF  ALCOHOLS  112 

A.  ALDEHYDES  112 

Oxidation  of  alcohol, — .  Aldehydes  not  hydroxyl  compounds, — .  Action  of 
PC1&, — .  Carbonyl  group, — .  Aldehyde  group, — .  Alcohol  an  oxidized 
hydrocarbon, — .  Two  hydroxyls  linked  to  one  carbon, — .  Addition  products 
of  aldehyde, — .  Aldol  condensation, — .  Acetal, — .  Polymerization, — .  Re- 
ducing properties, — .  Nomenclature, — . 

TABLE  XIII.  ALDEHYDES  AND  KETONES  119 

Formaldehyde — Methanal  119 

Acetaldehyde — Ethanal  120 

B.  KETONES  120 

Primary  alcohols  yield  aldehydes, — .  Secondary  alcohols  yield  ketones, — . 
Action  of  PC15  on  ketones, — .  Carbonyl  group  in  ketones, — .  Structure  of 
ketones, — .  Oxidation  of  primary  alcohols, — .  Oxidation  of  secondary 
alcohols, — .  Oxidation  of  tertiary  alcohols, — .  Distinguishing  reaction 
of  the  three  classes  of  alcohols, — .  Comparison  of  aldehydes  and  ketones, — . 
Names  of  ketones, — . 

Acetone — Propanone — Di-methyl  Ketone  124 

DERIVATIVES  OF  ALDEHYDES  AND  KETONES  124 

Oximes  and  Hydrazones  124 

C.  ACIDS  125 

Relation  to  alcohols, — .  Composition  and  constitution, — .  Action  of  metals, 
— .  Action  of  PCI 5, — .  Presence  of  methyl, — .  Oxidation  reactions, — . 
Stability  of  carbon-hydrogen  groups, — .  Scheme  of  relationships, — .  Homol- 
ogous series, — . 


xiv  CONTENTS 

PAGE 
TABLE  XIV.  HOMOLOGOUS  SERIES  SATURATED  ACIDS         131 

Names  of  acids, — .  Isomerism, — .  Preparation, — .  Properties, — .  Reac- 
tions,— .  Hydrocarbons  from  acids, — .  Ketones  from  acids, — . 

Formic  Acid — Methanoic  Acid  134 

Acetic  Acid — Ethanoic  Acid  135 

. 

Acetic  fermentation,— .  Vinegar, — .  Wood  distillation, — .  Glacial  acetic 
acid, — . 

Higher  Acids  136 

DERIVATIVES  OF  ACIDS  137 

i.  SALTS  137 

2.  ACID  CHLORIDES  137 

Acetyl  Chloride  137 

Acyl  radical, — .     Synthetic  use  of  acid  chlorides, — . 

3.  ACID  ANHYDRIDES  139 

Reaction  with  water, — .     With  alcohol, — .     With  ammonia, — . 

4.  ESTERS— ETHEREAL  SALTS  140 

Esterification,— .  Hydrolysis, — .  Saponification, — .  Names  'of  esters, — . 
Isomerism, — .  Preparation, — .  Properties  and  occurrence, — .  Fruit 
flavors, — .  Waxes  and  fats, — . 

5.  ACID  AMIDES  144 

Preparation  from  acid  chlorides, — .  From  esters, — .  From  ammonium 
salts, — .  Character, — .  Reaction  with  acids, — .  Reaction  with  bases, — . 
Tautomerism, — .  Reactions, — .  Hydrolysis, — .  Dehydration, — .  Hofmann's 
reaction, — . 

Acetamide  148 

Recapitulation  149 

.-V.. 

B.  SIMPLER  UNSATURATED  COMPOUNDS     w 

IV.  UNSATURATED  HYDROCARBONS  151 

GENERAL  15I 

Ethylene  or  ethene, — .  Addition, — .  Unsaturation, — .  Constitution  of 
ethylene, — .  Double  bond, — .  Other  types  of  addition, — . 

. 


CONTENTS  XV 

PAGE 

A.  ETHYLENE  OR  ETHENE  UNSATURATED  SERIES  157 

Homologous  series, — .     Isomers, — .     Chemical  properties, — .  » 

Ethylene— Ethene  158 

B.  ACETYLENE  OR  ETEtlNE  UNSATURATED  SERIES  159 

Triple  bond, — .     Homologous  series, — .     Names, — . 

Acetylene — Ethine  1 6 1 

C.  DI-ETHYLENE  HYDROCARBONS— DI-ENES  162 

Isoprene, — . 

D.  HYDROCARBONS  OF  GREATER  UNSATURATION  162 

Di-propargyl, — . 

V.  MONO-SUBSTITUTION  PRODUCTS  OF  UNSATURATED 

HYDROCARBONS  I04 

A.  HALOGEN  AND  CYANOGEN  SUBSTITUTION 

PRODUCTS  164 

VINYL  HALIDES— HALOGEN  ETHENES  164 
Vinyl  chloride, — . 

ALLYL  HALIDES,  CYANIDES,  ETC.  165 

Allyl     chloride,—.     Allyl     cyanide,—.     Allyl     iso-thio-cyanate,— .     Oil     of 
mustard, — . 

B.  UNSATURATED  ALCOHOLS  l66 

I.  ETHYLENE  SERIES  166 

Vinyl  Alcohol — Ethenol  1 6  6 

Allyl  Alcohol— Ai-Propenol-3  166 

Higher  Ethylene  Alcohols  167 
Geraniol, — . 

H.  ACETYLENE  SERIES  Z67 

Propargyl  alcohol, — . 

C.  ETHERS  AND  THIO-ETHERS  167 

Thio-ethers, — .     Oil  of  garlic, — . 


XVI  CONTENTS 

PAGE 

D.  UNSATURATED  ALDEHYDES  168 

Acrylic  Aldehyde— Acrolein  168 

Crotonic  Aldehyde — A2-Butenal  169 
Aldol  condensation, — . 

Higher  Ethene  Aldehydes  1 70 
Geranial, — . 

E.  UNSATURATED  ACIDS  170 

Synthesis, — .     Perkin-Fittig  synthesis, — . 

Acrylic  Acid — Propenoic  Acid  172 

Crotonic  Acid — A2-Butenoic  Acid  173 

alpha-Methyl  acrylic  acid, — .  Vinyl  acetic  acid, — .  Crotonic  and  iso- 
crotonic  acids, — .  Crotonic  acid  from  crotonic  aldehyde, — .  From  acetic 
aldehyde  and  malonic  acid, — .  Geometric  isomerism, — . 

Tiglic  Acid  and  Angelic  Acid  178 

Oleic  Acid  and  Elaidic  Acid  178 

One  double  bond, — .  Position  of  the  double  bond, — .  Conversion  of  oleic 
acid  into  elaidic  acid, — .  Iso-oleic  acid, — . 

Hypogaeic  Acid,  Linoleic  Acid,  Linolenic  Acid  180 

Propiolic  Acid — Propinoic  Acid  1 8 1 

C.     POLY-SUBSTITUTION  PRODUCTS  Ig2 

VI.  POLY-HALIDES,  CYANIDES  AND  AMINES  182 

A.  POLY-HALIDES  lg2 

I.  POLY-HALOGEN  METHANES  182 

Chloroform  183 

Chloroform  reaction, — .  Ortho  formic  acid, — .  Hofmann's  iso  nitrile  re- 
action,— . 

Bromoform  186 

lodoform  186 
lodoform  test  for  alcohol, — . 

Fluoroform  187 

Carbon  terra -chloride  187 


CONTENTS  XV11 

PAGE 

II.  POLY-HALOGEN  ETHANES  188 

Di-chlor  Ethanes  188 

Isomerism, — .     Unsymmetrical     di-chlor     ethane, — .     Symmetrical  di-chlor 
ethane, — .     EtHylene  and  ethylidene  compounds, — . 

Ethylidene  Halides  189 

Ethylidene  chloride, — . 

Ethylene  Halides  190 

Reactions, — . 

Higher  Halogen  Ethanes  192 

B.  POLY-CYANIDES  192 

C.  POLY-AMINES  193 

Putrescine  and  cadaverine, — .     Imines, — .     Heterocyclic  compounds, — . 

VII.  POLY-HYDROXY  COMPOUNDS— POLY-ALCOHOLS  195 

A.  DI-HYDROXY  ALCOHOLS— GLYCOLS  195 

Glycol  195 

Higher  Glycols  196 

DI-VALENT  MERCAPTANS— THIO-GLYCOLS  197 

Mercaptans  and  mercaptols, — .     Sulphonal, — . 

B.  TRI-HYDROXY  ALCOHOLS  198 

Glycerol  198 
Synthesis  from  propane, — .     Properties, — . 

DERIVATIVES  OF  GLYCEROL  200 

i.  SALTS         ,  200 

2.  ETHERS  200 

3.  OXIDATION  PRODUCTS  200 

Glycerose, — . 

4.  INORGANIC  ACID  ESTERS  201 

Hydrines, — .       Nitric     acid     esters, — .       Nitro-glycerin, — .       Dynamite, — . 
Nobel,—. 


xviii  CONTENTS 

PAGE 
5.  ORGANIC  ACID  ESTERS  203 

FATS  AND  OILS  203 

Acids  occurring  as  esters  in  fats  and  oils, — .  Constitution  of  fats  and  oils, — . 
Chevreul, — .  Reactions  of  fats  and  oils, — .  Hydrolysis, — .  Sapohification, 
— .  General  properties  of  fats  and  oils, — .  Glycerol  esters, — . 

TABLE  XV.  GLYCEROL  ESTERS,  FATS  AND  FATTY  ACIDS     208-209 
Analytical  methods, — . 

Physical  Constants  210 

Specific  gravity, — .  Melting  point  and  titer, — .  Refractive  index, — .  Re- 
fractometers, — .  Viscosity, — . 

Chemical  Constants  212 

Saponification  number, — .  Koetsttorfer  value,1 — .  Bromine  or  iodine  value, — . 
Hiibl-Wijs, — .  Insoluble  acids, — .  Hehner  value, — .  Volatile  acids, — . 
Reichert-Meissl  value, — .  Composition  of  butter  fat, — . 

TABLE  XVI.  CONSTANTS  OF  FATS  AND  OILS  216 

C.  HIGHER  POLY-HYDROXY  ALCOHOLS  217 

Erythritol,  Arabitol,  etc.  218 

Mannitol,  Dulcitol,  Sorbitol  219 

VIII.  MIXED  POLY-SUBSTITUTION  PRODUCTS         220 
GENERAL  220 

A.  MIXED  HALOGEN  AND  CYANOGEN  COMPOUNDS  220 

Halogens  only, — .  Halogens  and  nitro  group, — .  Chlor  picrin, — .  Halogens 
and  amino  group,—.  Halogens  and  cyanogen  group,—.  Cyanogen  and  amino 
compounds, — .  Cyanamide, — . 

B.  MIXED  HYDROXY  COMPOUNDS— SUBSTITUTED 

ALCOHOLS  222 

I.  HALOGEN  ALCOHOLS  222 

Halogen  hydrines, — .     Epi-chlor  hydrines, — . 

H.  AMINO  ALCOHOLS  22S 

m.  CYANOGEN  ALCOHOLS  225 


CONTENTS  XIX 

PAGE 

C.  SUBSTITUTED  ALDEHYDES  AND  KETONES        226 

I.  HALOGEN  ALDEHYDES  226 

Tri-chlor  Aldehyde— Chloral  2  2  6 

H.  HALOGEN  KETONES  228 

HI.  HYDROXY  ALDEHYDES  AND  HYDROXY  KETONES  228 

Aldehyde-alcohols, — .     Ke  tone-alcohols, — . 

Glycolic  Aldehyde  and  Glyceric  Aldehyde  229 

Aldol  229 

Aldol  condensation, — . 

D.  SUBSTITUTED  ACIDS  229 

I.  HALOGEN  ACIDS  230 

Halogenation  of  acids, — .  Nomenclature  of  substituted  acids, — .  General 
properties, — .  Reactions, — .  alpha-,  beta-  and  gawraa-acids, — .  Inner 
anhydrides, — . 

Chlor  Formic  Acid  234 

Chlor  Acetic  Acids  234 

H.  HYDROXY  ACIDS  236 

Syntheses,—.  Alcohol-like  syntheses, — .  From  halogen  acids, — .  From 
amino  acids, — .  Acid-like  syntheses, — .  From  cyan  hydrines, — .  From 
poly-hydroxy  alcohols, — .  From  unsubstituted  acids, — .  Reactions  and 
products, — .  Ethers, — .  Esters  with  acids, — .  Esters  with  alcohols, — -. 
Ether-esters, — .  Mixed  esters, — .  Anhydrides, — .  alpha-Hydroxy 
acid  anhydrides, — .  6e/a-Hydroxy  acid  anhydrides, — .  gamma-Hydroxy 
acid  anhydrides, — .  Reduction, — . 

Hydroxy  Formic  Acid  244 

Hydroxy  Acetic  Acid  244 

Hydroxy  Propionic  Acids  245 

Hydracrylic  Acid  245 

Synthesis  from  acrylic  acid, — .     From  propionic  acid, — .  From  ethylene, — . 

Lactic  Acid  246 

Reactions, — .  Anhydrides, — .  Pyro-racemic  acid, — .  Stereo-isomerism, — . 
Inactive  or  fermentation  lactic  acid, — .  Dextro  lactic  acid, — .  Sarco  lactic 
acid, — .  Levo  lactic  acid, — .. 


XX  CONTENTS 

PAGE 
HI.  ALDEHYDE  ACIDS  AND  KETONE  ACIDS  251 

ALDEHYDE  ACIDS  252 

Glyoxylic  Acid  252 

Formyl  Acetic  Acid  253 

Glucuronic  or  Glycuronic  Acid  253 

KETONE  ACIDS  253 

Pyro-racemic  or  Pyruvic  Acid  253 

Synthesis  from  acetyl  chloride, — .  From  a-a-di-brom  propionic  acid, — . 
From  lactic  acid, — .  From  acetic  and  formic  acids, — 

Ac  eto  Ac  etic  Acid  254 

Preparation  of  ethyl  aceto  acetate, — .  Tautomerism, — .  Enol  and  keto 
forms,—.  Ketone  hydrolysis, — .  Acid  hydrolysis,—.  Sodium  salt, — . 
Alkyl  derivatives, — .  Aceto  acetic  ester  syntheses, — .  Action  of  ammonia — . 

Levulinic  Acid  260 

IX.  POLY-ALDEHYDES,  POLY-KETONES  AND  POLY- 

CAKBOXY  ACIDS  261 

A.  D  I- ALDEHYDES  AND  DI-KETONES  261 

I.  DI-ALDEHYDES  261 

Glyoxal  261 

II.  DI-KETONES  261 

i-2-DI-KETONES,  Di-acetyl  262 

From  aceto  acetic  ester, — .     Iso-nitroso  and  oxime  compounds, — . 

i-3-DI-KETONES,  Acetyl  Acetone  263 

From  ethyl  acetate, — . 

B.  POLY-CARBOXY  ACIDS  264 

I.  SATURATED  DI-BASIC  ACIDS  264 

Oxalic  Acid  264 

Synthesis  from  cyanogen,—.  Hydrolysis  of  cyanogen, — .  From  glycol, — . 
From  hexa-chlor  ethane,—.  Oxidation  products  of  ethane,—.  Relation 
to  formic  acid, — .  Reduction  of  carbon  dioxide, — .  Commercial  prepara- 
tion,— .  Goldschmidt  process, — .  Properties  of  oxalic  acid, — . 


CONTENTS  XXI 

PAGE 
Derivatives  of  Oxalic  Acid  271 

Salts, — .     Esters, — .     Acid  chlorides, — .     Acid  amides, — . 

Malonic  Acid  273 

Relation  to  propane, — .     Relation  to  methane  and  acetic  acid, — .     Homo- 

logues, — .     Reactions, — .     Malonic  acid  syntheses, — .  Derivatives  of  malonic 
acid, — . 

Homologues  of  Malonic  Acid  278 

SuccinicAcid  278 

Synthesis  from  ethylene  bromide, — .     From  brom  acetic  acid, — .     Di-acelic 
acid, — .     Succinic  acid  from  malonic  ester, — .     Properties  of  succinic  acid, — . 

Derivatives  of  Succinic  Acid  280 

Salts, — .     Anhydride, — .     Acid  chlorides, — .     Acid  amides, — •.     Imide, — . 

Homologues  of  Succinic  Acid  284 

Glutaric  Acid  285 

Synthesis    from    propane, — .     From    aceto    acetic    ester, — .     From    malonic 
ester, — .     Glutaric  anhydride, — . 

Higher  Dibasic  Acids  288 

Adipic  acid, — .     Suberic  acid, — . 

II.  UNSATURATED  DI-BASIC  ACIDS  289 

Maleic  Acid  and  Fumaric  Acid  290 

Synthesis  from  succinic  acid, — .     Isomerism  of  maleic  and  fumaric  acids, — . 
Conversion  into  each  other, — . 

Citra-conic,  Mesa-conic,  Ita-conic  Acids  293 

Citra-conic  and  mesa-conic  acids,—.     Ita-conic  acid, — . 

HI.  HYDROXY  DI-BASIC  ACIDS  295 

HYDROXY  MALONIC  ACIDS  296 

Tartronic  Acid  296 

Synthesis  from  malonic  acid, — .     From  glycerol, — . 

Mesoxalic  Acid  296 

HYDROXY  SUCCINIC  ACIDS  297 

Malic  Acid  297 

Relation  to  succinic  acid, — .     To  maleic  and  fumaric  acids, — .     Stereo-isomer- 
ism  of  malic  acid, — .     Active  malic  acid, — .     Inactive  malic  acid, — . 


XX11  CONTENTS 


PAGE 
Tartaric  Acid  301 

Di-basic  and  di-alcoholic,— .  Symmetrical,—.  Synthesis  from  glyoxal— . 
From  succinic  acid, — .  From  malic  acid, — .  From  maleic  and  fumaric 
acids, — .  Reduction  to  malic  and  succinic  acids, — .  Isomerism  of  tartaric 
acid,—.  Historical,—.  Pasteur,—.  Splitting  of  racemic  compounds,—. 

Dextro  Tartaric  Acid  309 

Salts, — .     Acid  potassium  tartrate, — .     Rochelle  salt, — .  Tartar  emetic, — . 

Levo  Tartaric  Acid  311 

Racemic  Acid  3 1 1 

Meso  Tartaric  Acid  312 

IV.  TRI-BASIC  ACIDS  AND  HYDRO XY  TRI-BASIC  ACIDS          312 

Tri-carballylic  Acid  and  Aconitic  Acid  3 1 2 

Citric  Acid  313 

Synthesis  from  glycerol, — .  From  aceto  acetic  ester, — .  Salts, — .  Neutral 
ammonium  citrate, — ,  Magnesium  citrate, — .  Ferric  ammonium  citrate, — . 
Ferric  citrate, — . 

X.  CARBOHYDRATES  316 

GENERAL  316 

Oxidation  products  of  poly-hydroxyl  alcohols, — .  Composition  and  constitu- 
tion,— .  Alcohol  compounds, — .  Esterification  or  acetylation, — .  Number 
of  hydroxyl  groups, — .  Aldehyde  and  ketone  compounds, — .  Aldehyde  and 
ketone  reactions, — .  Synthesis, — •.  Glycerose, — .  Reduction  of  carbohy- 
drates,— .  Straight  chain  compounds, — .  Position  of  aldehyde  group, — . 
Position  of  ketone  group, — .  Constitution, — . 

Derivatives  of  Carbohydrates  and  Conversion  of  Carbohydrates  325 

Oxidation  to  acids, — .  Phenyl  hydrazine  reaction, — .  Hydrazones, — . 
Osazones, — .  Glucosazone, — .  Fructosazone, — .  Osones, — .  Conversion  of 
aldose  to  ketose, — .  Increasing  carbon  content  of  aldoses,— .  Decreasing 
carbon  content  of  aldoses, — . 

Reactions  of  Carbohydrates  331 

Fermentation, — .     Reduction  of  Fehling's  solution, — . 

Chemical  Classification  of  Carbohydrates  333 

Mono-saccharoses, — .  Poly-saccharoses, — .  Di-saccharoses  or  hexo-bioses, — . 
Tri-saccharoses  or  hexo-tri-oses, — .  Poly-saccharoses,  not  true  sugars, — . 
Summary  of  classification, — . 


CONTENTS  XX111 

PAGE 

A.  MONO-SACCHAROSES  336 

I.  BIOSES  336 

H.  TRIOSES  336 

Glycerose, — . 

IH.  TETROSES  337 

Erythrose, — . 

IV.  PENTOSES  338 

Pentosans, — 

Arabinose  339 

Xylose  *                                              339 

Rhamnose  339 

V.  HEXOSES  339 

Synthesis  from  poly-alcohols, — .  From  glycerose, — .  From  formaldehyde, — . 
Hydrolysis  of  poly-saccharoses, — . 

Stereo-isomerism  of  the  Mono-saccharoses  342 

Number  of  stereo-isomers, — .     Table  of  stereo-isomers  of  glucose, — . 

Lactone  Constitution  of  Glucose  345 

Muta  rotation, — .  alpha-  and  beta-Methyl  glucosides, — .  alpha-  and  beta- 
Glucoses, — .  Lactone  formula, — .  Explanation  of  isomeric  glucoses  and 
glucosides, — .  Explanation  of  muta  rotation, — .  Oxonium  compounds,' — . 

Glucose — Dextrose — Grape  Sugar  351 

Galactose  351 

Fructose — Levulose — Fruit  Sugar  352 
Invert  sugar, — .     Inversion, — . 

B.  DI-SACCHAROSES  353 

Sucrose — Cane  Sugar  353 

Constitution  of  sucrose, — .  Sources, — .  Industrial  processes, — .  Extrac- 
tion of  juice, — .  Diffusion  process, — .  Concentration, — .  Evaporation, — . 
Crystallization, — .  Refining, — .  History  and  statistics, — .  Analysis, — . 

Lactose— Milk  Sugar  358 

Maltose — Malt  Sugar  360 

Malt, — .     Alcoholic  fermentation, — . 


XXIV  CONTENTS 

PAGE 

C.  TRI-SACCHAROSES  361 

Raffinose  361 

D.  POLY-SACCHAROSES  (not  sugars)  36i 

General  character, — .     Solubility, — .     Iodine  reaction, — .     Enzyme  action, — . 

Starch  363 

Photosynthesis, — .     industrial  uses, — .     Isolation  of  starch, — . 

Cellulose  366 

Normal  cellulose, — .  Hemi-cellulose, — .  Compound  celluloses, — .  Ligno- 
cellulose, — .  Pecto-cellulose, — .  Adipo-cellulose, — .  Properties  of  cellulose, — . 
Schweitzer's  reagent, — .  Xanthic  acid, — .  Amyloid, — ,  Cellobiose, — .  Nitro 
cellulose, — .  Constitution, — . 

Industrial  Uses  of  Cellulose  369 

Cotton  and  linen  cloth,  etc., — .  Paper, — .  Wood  pulp, — ...  Production 
and  consumption  of  paper, — .  Parchment  paper, — .  Mercerized  cotton, — . 
Artificial  silk, — .  Viscose  silk, — .  Nitric  acid  esters, — .  Pyroxylin, — . 
Collodion, — .  Pyro-collodion, — .  Gun  cotton, — .  Celluloid, — .  Cellulose  ex- 
plosives,— .  Gun  cotton, — .  Nitration  of  cellulose, — .  Cordite, — .  Smoke- 
less powders,  etc., — .  Explosive  force  of  explosives, — . 

Dextrin,  Glycogen,  Inulin  379 

Mannans  and  Gallactans  380 

TABLE  XVII.  SUMMARY  OF  CARBOHYDRATES  381 

XI.  AMINO  ACIDS  AND  PROTEINS  382 

A.  AMINO  ACIDS  382 

Synthesis  from  halogen  acids, — .  From  aldehydes, — .  From  oximes  and 
hydrazones, — .  From  proteins, — .  Acid  and  basic, — .  Esters, — .  Primary 
amines, — .  Salts, — .  Inner  salts, — .  Anhydrides, — . '  Di-keto  piperazines, — . 
Poly-peptides,- — . 

I.  MONO-AMINO  ACIDS  DERIVED  FROM  MONO-BASIC  ACIDS  388 

Glycine,  Amino  Acetic  Acid  388 
Sarcosine,  Betaine, — .     Hippuric  acid, — . 

Di-amino  Acetic  Acid  389 

Alanine  389 


CONTENTS  XXV 

PAGE 
Serine  389 

Cysteine  389 

Cystine  389 

Phenyl  Alanine  389 

Tyrosine  389 

Tryptophane  389 

Histidine  390 

alpha-Ammo  Butyric  Acid  390 

Valine  390 

alpha-Ammo  Valeric  Acid  390 

Leucine  390 

Iso  Leucine  390 

Caprine  390 

II.  DI-AMINO  ACIDS  DERIVED  FROM  MONO-BASIC  ACIDS       391 

Arginine  391 

Lysine  391 

III.  MONO-AM1NO  ACIDS  DERIVED  FROM  DI-BASIC  ACIDS      391 

Aspartic  Acid  391 

Asparagine, — . 

Glutamine  391 

Proline  392 

Oxy  Proline  392 

Di-amino  Di-hydroxy  Suberic  Acid  392 

Di-amino  Tri-hydroxy  Dodecanoic  Acid  392 

B.  PROTEINS  392 

Composition, — .  Molecular  weight, — .  Physical  properties,- — .  '  Non-crystal- 
line,— .  Solubility, — .  Chemical  properties,' — .  Amnio  nitrogen, — .  Hydrol- 
ysis of  proteins, — .  Simple  proteins, — .  Conjugated  proteins, — .  Derived 
proteins, — .  Classification, — .  Common  proteins, — .  Egg  albumin, — .  Blood 
albumin, — .  Milk  albumin, — .  Blood  serum  globulin, — .  Egg  globulin, — . 
Milk  globulin, — .  Plant  globulins, — .  Edestin, — .  Excelsin, — .  Glutenin, — . 
Gliadin— .  Zein,— .  Hordein— .  Collagen,—.  Elastin,— .  Keratin,—. 
Globin, — .  Salmine, — .  Sturine, — .  Caseinogen, — .  Ova-vitellin, — . 
Haemoglobin, — . 


XXVI  CONTENTS 

PAGE 
Classification  of  Proteins  398 

Simple  proteins, — .  Albumins, — .  Globulins, — .  Glutelins, — .  Prolamins, — . 
Albuminoids, — .  Histones, — .  Protamines, — .  Conjugated  proteins, — . 
Nucleo-proteins, — .  Glyco-proteins, — .  Phospho-proteins, — .  Haemo-glo- 
bins,— .  Lecitho-proteins, — .  Derived  proteins, — .  Primary, — .  Proteans, 
— .  Meta-proteins, — .  Coagulated  proteins, — .  Secondary, — .  Proteoses, — . 
Peptones, — .  Peptides  or  poly-peptides, — . 

POLY-PEPTIDES  AND  THE  CONSTITUTION  OF  PROTEINS      399 

Analytical  and  synthetical  study  of  proteins, — .  Alanyl  alanine, — .  Glycyl 
alanine, — .  Alanyl  glycine, — .  alpha-Ammo  acids, — .  Stereo-isomers, — . 
Tautomerism  of  poly-peptides  and  proteins, — . 

Hydrolysis  by  Enzymes  404 

Proteolytic  enzymes, — . 

Qualitative  Tests  405 

Color  reactions, — .  Millon's  reaction, — .  Biuret  reaction, — .  Xanthoproteic 
reaction,' — .  Precipitation  tests, — .  Precipitated  proteins, — .  Metal  albu- 
minates, — .  Precipitated  meta-proteins, — .  Soluble  acid  albuminates, — . 
Precipitated  protein  salts, — . 

XII.  CYANOGEN,  CYANIDES,  CYANATES  408 

A.  CYANOGEN  OR  DI-CYANOGEN  408 

B.  HYDROCYANIC  ACID  AND  SALTS  409 

Hydrocyanic  Acid— Hydrogen  Cyanide  409 

Metal  Cyanides  410 

Potassium  cyanide, — -.  Silver  cyanide, — .  Constitution  of  hydrocyanic  acid 
and  its  salts) — .  Synthesis  from  cyanogen, — .  From  acetylene, — .  From 
ammonia, — .  Alkyl  cyanides  from  potassium  cyanide, — .  Alkyl  iso-cyanides 
from  silver  cyanide, — .  Tautomerism, — .  Ferrous  and  ferric  cyanides, — . 
Hydro-ferro-cyanic  and  hydro-ferri-cyanic  acids, — .  Potassium  salts, — .  Iron 
salts, — .  Potassium  ferro-cyanide, — . 

C.  CYANIC  ACID,  ISO-CYANIC  ACID,  THIO-CYANIC 

ACID  AND  SALTS  4l6 

Cyanic  and  Iso-cyanic  Acids  and  Salts  416 

Iso-cyanic  acid, — .  Potassium  cyanate, — .  Ammonium  cyanate, — .  Cya- 
nuricacid, — .  Fulminic  acid, — .  Bi-valent  carbon, — .  Mercuric  fulminate, — . 


CONTENTS  XXV11 

PAGE 
Thio-cyanic  Acid  and  Salts  420 

Iso-thio-cyanates, — . 

Cyanogen  Chloride  and  Cyanamide  421 

Cyanogen  chloride, — .  Cyanamide, — .  Calcium  cyanamide, — .  Fixation 
of  atmospheric  nitrogen, — .  Source  of  cyanides  and  ammonia, — .  Fertilizer — . 
Sodium  cyanide  from  atmospheric  nitrogen, — . 

XIII.  CARBONIC  ACID,  UREA,  URIC  ACID,  PURINE 

BASES,  ETC.  425 

A.  CARBONIC  ACID  AND  DERIVATIVES  425 

Carbonic  Acid  425 

Carbonates, — .  Carbonic  acid, — .  Carbon  dioxide — .  Constitution, — . 
Carbonyl  chloride, —  Ethyl  chlor  formate, —  Di-ethyl  carbonate, — .  Phos- 
gene,— . 

B.  UREA  AND  DERIVATIVES  429 

Urea— Carbamide  429 

Carbamide, — .  Carbamic  acid, — .  Urethane, — .  Biological  synthesis  and 
decomposition, — .  Wohler's  synthesis, — .  Occurrence  and  properties/ — . 
Biuret, — .  Enzymatic  hydrolysis  of  urea, — .  Hypobromite  reaction,- — . 
Clinical  test, — .  Salts, — .  Isolation  of  urea  from  urine, — .  Alkyl  ureas, — . 

Thio-ureas  437 

Ureids  437 

Cyclic  ureids,— .  Parabanic  acid,—.  Hydantoin  — .  Barbituric  acid,—. 
Di-aluric  acid, — .  Iso-dialuric  acid, — .  Alloxan, — .  Allantoin, — . 

Imino  Derivatives  of  Urea  439 

Guanidine,— .  Guanine,— .  Guano,—.  Semi-carbazid,— .  Creatine  and 
creatinine — . 

C.  URIC  ACID  442 

Constitution, — .  Medicus'  formula, — .  Methyl  uric  acids/ — .  Fischer, — . 
Horbaczewski's  synthesis  of  uric  acid, — .  Behrend  and  Roosen's  synthesis, — . 
Properties, — . 

PHYSIOLOGICAL  RELATION  OF  UREA,  URIC  ACID,  ETC.         446 
Urine  nitrogen, — .     Urine  analysis, — .     Sugar  and  albumin  in  urine, — . 

D.  PURINE  BASES  448 

Purine,— .  Xanthine,— .  Uric  acid,—.  Theobromine,— .  Caffeine,—. 
Theine, — .  Guanine, — . 


xxviii  CONTENTS 

PART  II 
CYCLIC  COMPOUNDS 

PAGE 

INTRODUCTION  AND  RESUMfi  OF  ALIPHATIC  SERIES         453 
RING  COMPOUNDS  OF  THE  ALIPHATIC  SERIES  453 

Hetero-cyclic  compounds, — .     Carbo-cyclic  compounds, — .     Benzene, — . 

SECTION  I.     CARBO-CYCLIC  COMPOUNDS     46o 

A.  ALI-CYCLIC  COMPOUNDS  46o 

i.  SATURATED  ALI-CYCLIC  COMPOUNDS     46o 

Tri-methylene  or  cyclo-propane, — .  Poly-methylenes  or  cyclo-paraffins, — . 
Ali-cyclic  compounds, — . 

2.  UNSATURATED  ALI-CYCLIC  COMPOUNDS  462 

Strain  Theory  of  Carbo-cyclic  Compounds  462 

B.  CARBO-CYCLIC  COMPOUNDS  DERIVED 
FROM  BENZENE,  ISO-CYCLIC  COMPOUNDS  OR 
AROMATIC  COMPOUNDS  466 

i.  BENZENE  SERIES  466 

A.  HYDROCARBONS  466 

Constitution  of  Benzene  466 

Aromatic  compounds, — .  Benzene  series, — .  Benzene, — .  Coal  tar,—. 
Light  oil, — .  C6H6,  CnH2n_6, — .  Di-propargyl, — .  Benzene  and  bromine, — . 
Hexa-hydro  benzene, — .  Cyclo-hexane, — .  Hexagon  formula, — .  Properties 
of  benzene, — .  Substitution  products, — .  Nitro  products/ — .  Sulphonic 
acids, — .  Homologues  oxidized, — .  Halogen  products, — .  Hydroxyl  prod- 
ucts,— . 

Isomerism  471 

Mono-substitution  products, — .  Symmetry  of  benzene, — .  Hexagon  formula, 
— .  Di-substitution  products, — .  Tri-substitution  products/— .  Ortho,  meta, 
para, — .  Vicinal,  symmetrical,  unsymmetrical, — .  Position  isomerism, — . 
Hexagon  theory  and  tetra- valence  of  carbon, — .  Kekule  formula,' — .  Oscilla- 
tion theory, — .  Ladenburg  formula, — .  Formulas  of  Claus,  Armstrong  and 
Baeyer, — .  Benzene  hexagon  in  space, — .  Homologous  series, — . 


CONTENTS  XXIX 

PAGE 
Benzene  477 

Coal  tar, — .  Preparation  from  benzole  acid, — .  Synthesis  of  benzene  and 
homologues, — .  Benzene  from  acetylene, — .  Mesitylene  from  allylene, — . 

Toluene  479 

Fittig's  synthesis, — .  Friedel-Craft  reaction, — .  Ease  of  substitution, — . 
Oxidation, — . 

Xylenes  480 

Isomeric  xylenes,— .  Ethyl  benzene, — .  Orientation, — .  ortho-,  meta-  and 
^ara-Xylene, — .  />ara-Xy]ene, — .  ortho-Xy\ene, — .  we/a-Xylene, — .  Oxi- 
dation of  xylene, — . 

Hydrocarbons,  C9Hi2  486 

Tri-methyl  benzenes, — .  Mesitylene, — .  Oxidation  of  methylene, — .  Syn- 
thesis from  allylene, — .  From  acetone, — .  Substitution  products  of  mesity- 
lene, — .  Pseudocumene, — .  Synthesis  from  brom  />ara-xylene  and  from 
brom  we/a-xylene, — .  Hemelithene, — .  Propyl  and  iso-propyl  benzenes. — . 

Hydrocarbons,  CioHu  491 

Durene, — .     Cymene, — . 

Hydrocarbons,  CnH2n_8  and  CnH2n_10  493 

Styrene, — .     Phenyl  propene, — .     Phenyl  acetylene, — . 

COM,  TAR  494 

Illuminating  gas, — .  Distillation  of  coal, — .  Gaseous  products, — .  Liquid 
and  solid  products, — .  Coal  tar, — .  Composition  of  illuminating  gas, — . 
Gas  liquor  salt, — .  Ammonium  sulphate, — .  Coke, — .  Fractional  distilla- 
tion of  coal  tar, — .  Light  oil, — .  Middle  oil, — .  Heavy  oil, — .  Anthracene 
oil, — .  Pitch  or  tar, — .  Fractional  distillation  of  light  oil,  — .  90  per  cent 
benzene, — .  50  per  cent  benzene, — .  Yield  from  coal  tar, — .  Coal  tar  in- 
dustry,— .  Theories  of  formation  of  benzene, — . 

B.  DERIVATIVES  OF  BENZENE  HYDROCARBONS       502 

I.  HALOGEN  DERIVATIVES  502 

HALOGEN  BENZENES  503 

Hexa-hydro  benzene, — .  Benzene  hexa-chloride, — .  Halogen  substitution 
products, — .  Reactions, — .  Fittig's  reaction, — .  Benzene  from  mono-halo- 
gen benzene, — . 

TABLE  XVIII.  HALOGEN  SUBSTITUTION  PRODUCTS  OF  BENZENE  507 

lodo  benzene, — .  Tri-valent  and  penta-valent  iodine, — .  Phenyl  iodoso 
chloride, — .  Iodoso  benzene, — .  Phenyl  iodonium  hydroxide/ — .  lodoxy 
benzene, — .  Di-phenyl  iodonium  hydroxide, — .  Iodonium  hydroxide, — . 


XXX  CONTENTS 

PAGE 
HALOGEN  SUBSTITUTION  PRODUCTS  OF  BENZENE  HOMOLOGUES  509 

Substitution  in  the  ring, — .  In  the  side-chain, — .  Chlorine  substitution 
products  of  toluene, — .  Chlor  toluenes, — .  Oxidation  products, — .  Isomer- 
ism, — .  Halogen  substitution  products  of  higher  homologues, — . 

II.  SULPHURIC  AND  SULPHUROUS  ACID  DERIVATIVES  514 

SULPHONIC  ACIDS  514 

Sulphuric  acid  derivatives, — .  Esters,—.  Sulphonic  acids, — .  Prepara- 
tion> — .  Sulphonic  acids  of  benzene  homologues, — .  Toluene  sulphonic 
acids,—.  Acid  character  of  sulphonic  acids,—.  Salts,—.  Reactions  of 
sulphonic  acids, — .  Sulphon  chlorides,  — .  Sulphon  amides, — .  Esters  of  sul- 
phonic acids, — .  Sulphonic  acids  to  hydroxyl  compounds, — .  Cyanides  or 
nitriles, — .  Acids  from  sulphonic  acids, — .  Hydrolysis  of  sulphonic  acids, — . 
Reactions  of  di-sulphonic  acids, — .  Summary  of  reactions, — . 

SULPHINIC  ACIDS  523 

Sulphurous  acid  derivatives, — .  Sulphinic  acids, — .  Sulphones, — .  Formula 
for  sulphinic  acids, — .  Desmotropism, — .  Thio-sulphonic  acids, — . 

SULPHONES  526 

Synthesis,—. 

III.  NITRIC  AND  NITROUS  ACID  DERIVATIVES      528 

NITRO  COMPOUNDS  528 

Not  acids, — .  Not  esters, — .  Non-hydrolyzable, — .  Reduction, — .  Di-  and 
tri-nitro  products, — .  Homologous  nitro  compounds, — . 

Nitro  Benzenes  530 

Mono-nitro  benzene, — .     Di-nitro  benzene, — .     Tri-nitro  benzene, — . 

Nitro  Toluenes  531 

Tri-nitro  toluene,  T.N.T., — .  Amatol, — .  Ammonal, — .  Faversham 
powder, — . 

Nitro  Xylenes  534 

Nitro  alkyl  benzenes, — . 

REDUCTION  PRODUCTS  OF  NITRO  BENZENE  535 

Reduction  of  nitric  acid, — .  Reduction  of  nitro  benzene  with  alcohol  and 
zinc, — .  Phenyl  hydroxylamine, — .  With  acid  and  zinc, — .  Nitroso  ben- 
zene,— .  With  alcoholic  alkali  and  zinc, — .  With  aqueous  alkali  and  zinc, — . 
Azo  benzene, — .  Hydrazo  benzene, — . 

NITROSO  COMPOUNDS  538 

Nitroso  benzene, — . 


CONTENTS  XXXI 

PAGE 

IV.  AMMONIA  DERIVATIVES  OR  AMINES  S39 

Aniline  539 

History, — .  Substituted  ammonia, — .  Preparation, — .  Aniline  dyes, — .  Re- 
actions of  aromatic  amines  with  acids, — .  With  nitrous  acid, — .  Diazo 
benzene, — .  With  carbon  di-sulphide, — .  With  organic  acids, — .  Anilides, — . 

Toluidines  and  Xylidines  544 

Homologous  amines, — .  Toluidines, — .  Dyes, — .  Xylidines, — .  Technical 
xylidine, — .  Pseudocumidine, — . 

DERIVATIVES  OF  AROMATIC  AMINES  545 

i.  ALKYL  AND  ARYL  ANILINES  546 

Reactions  with  nitrous  acid, — .  Primary  amines, — .  Secondary  amines, — . 
Phenyl  nitroso  amine, — .  Tertiary  amines, — .  Reactions  with  acids  and 
with  alkyl  halides, — .  Reaction  with  acetyl  chloride, — . 

Mono -methyl  Aniline,  Di -methyl  Aniline  550 

Mono-methyl  aniline, — .  Nitroso  amine, — .  £ara-Nitroso  methyl  aniline, — . 
Di-methyl  aniline, — .  £ara-Nitroso  di-methyl  aniline, — .  Methyl  violet, — . 
Rearrangement  of  alkyl  anilines. — . 

Di-phenyl  Amine,  Tri-phenyl  Amine  554 

2.  SALTS,  ANILIDES,  ETC.  555 

Acetaniiide  556 

Antifebrin,— .     Di-anilides, — . 

3.  SUBSTITUTED  ANILINES,  ETC.  557 

Halogen  Anilines  557 

Nitroso  Anilines  558 

Nitro  Anilines  559 

Sulphonic  Acid  Derivatives,  Sulphanilic  Acid  560 

Inner  salt  constitution, — . 

4.  ANILINO  ACIDS  561 

Phenyl  Glyciue  561 

Phenyl  glycine,  Anilino  acetic  acid, — . 

POLY-AMINO  BENZENES  561 

Di-amino  Benzenes,  Phenylene  Di-amines  561 

para-Ammo  Di-methyl  Aniline  562 
Relation  to  dyes, — . 


XXxii  CONTENTS 

PAGE 

V.  NITROGEN  COMPOUNDS  BETWEEN  NITRO 

BENZENE  AND  ANILINE  563 

Phenyl  Hydroxyl  Amine  563 

Oxidation  products, — .     Phenyl  nitroso  hydroxyl  amine, — .     Molecular  re- 
arrangement to  para-ammo  phenol, — .     Benzyl  hydroxyl  amine, — . 

Azoxy  Benzene  565 

Rearrangement, — . 

Azo  Benzene  566 

From  nitroso  benzene  and  aniline, — .     Homologous  azo  compounds, — .     Azo 
compounds, — .     Di-azo  compounds, — .     Di-azo  reaction, — . 

DERIVATIVES  OF  AZO  COMPOUNDS  569 

AMINO  AZO  COMPOUNDS  569 

Griess  di-azo  reaction, — .     Di-azo  amino  compounds, — .     Ammo  azo  benzene 
from  nitro  azo  benzene, — .     Constitution, — . 

Amino  Azo  Benzene  5  73 

Aniline  yellow, — .     Acid  yellow, — . 

Di-methyl  Amino  Azo  Benzene  573 

Butter  yellow, — .     Methyl  orange, — . 

Di-amino  Azo  Benzene  574 

Chrysoidine, — . 

Tri-amino  Azo  Benzene  574 

Bismarck  brown, — . 

HYDROXY  AZO  COMPOUNDS  576 

Azo  dyes, — . 

HYDRAZO  COMPOUNDS  577 

Hydrazo  Benzene  577 

Oxidation    and    reduction, — .     Secondary   amines, — .     Molecular    rearrange- 
ment,— .     Benzidine, — .     Benzidine  dyes, — . 

HYDRAZINES  579 

Derivatives  of  di-amide, — .     Symmetrical  and  unsymmetrical  hydrazines/ — . 

Phenyl  Hydrazine  580 

Carbohydrate    reagent, — .      Oxidizing    agent, — .      Osazones, — .      Reducing 
agent, — .     Tri-azo  compounds, — .     Derivatives  of  phenyl  hydrazine, — . 


CONTENTS  XXX111 

PAGE 

VI.  DI-AZO  COMPOUNDS  585 

Peter  Griess, — .     Diazotization, — . 

Di-azo  Benzene — Benzene  Diazonium  Chloride  587 

Constitution, — .  Bases, — .  Neutral  salts, — .  Griess  formula, — .  Kekule" 
formula, — .  Bloomstrand,  Strecker,  Erlenmeyer  formula, — .  Tautomerism, — . 
Acids,  alkali  salts, — .  Diazotates, — .  Isomerism, — .  Hantzsch  stereo 
formula, — .  Syn,  anti, — .  Phenyl  nitroso  amine, — .  Benzene  di-azo  sul- 
phonic  acid, — .  Di-azo  esters, — . 

Reactions  of  Di-azo  Compounds  595 

Reduction  to  hydrocarbons, — .  Oxidation, — .  Reaction  with  water  yields 
phenols, — .  Alcohols  yield  ethers, — .  Sulphur  compounds, — .  Halogen 
acids  yield  aromatic  halides, — .  Sandmeyer  reaction, — .  Gattermann  re- 
action,— .  Cyanides  yield  nitriles, — .  Aromatic  acids, — . 

TABLE  XIX.  REACTIONS  OF  DI-AZO  COMPOUNDS      600-603 
Resume  of  Nitrogen  Derivatives  604 

VII.  HVDROXYL  DERIVATIVES  606 

A.  PHENOLS  606 

Phenols, — .     Alcohols, — .     Mono-  and  poly-phenols, — . 

Synthesis  608 

From  sulphonic  acids, — .  From  di-azo  compounds, — .  From  hydrocarbons, — . 
From  hydroxy  acids, — .  From  aryl  halides,  — .  From  natural  sources, — . 

Properties  and  Reactions  610 

Salts, — .  Esters, — .  Ethers, — .  Reaction  with  phosphorus  penta-chloride,— . 
With  ammonia, — .  Reduction  and  oxidation, — .  Substitution  in  the  ring,- — . 
Color  reactions, — .  Liebermann's  nitroso  reaction, — . 

MONO-PHENOLS,  MONO-HYDROXY  BENZENES  613 

Phenol,  Carbolic  Acid  613 

Poison  and  anti-septic, — .     Commercial  preparation, — . 

Cresols  614 

Tri-cresol,— . 

Carvacrol  and  Thymol  615 

Terpenes'and  camphor, — . 

POLY-PHENOLS,  POLY-HYDROXY  BENZENES  616 

Di-hydroxy  Benzenes  6 1 6 

Pyrocatechinol, — .  Guaiacol, — .  Resorcinol, — .  Fluorescein, — .  Orcinol, — . 
Litmus, — .  Hydroquinol, — . 


CONTENTS 

PAGE 
Tri-hydroxy  Benzenes  619 

Pyrogallol,— .    Use  in  gas  analysis,—.    Photographic  developer,—.     Phloro- 
glucinol, — .    Pentosan  reagent, — .     Constitution,—.     Tautomerism,— . 

DERIVATIVES  OF  PHENOLS  621 

Phenol  Ethers  621 

Guaiacol,— .     Phenols  with  unsaturated  side  chain,—.     Isomerism,— .     Anol 
and  anethole,— .     Chavicol  and  estragole,— .     Eugenole  and  safrole,— . 

SUBSTITUTED  PHENOLS  624 

General  methods  of  synthesis, — . 

Halogen  Phenols  625 

Phenol  Sulphonic  Acids  626 

Nitroso  Phenols  627 
Quinone  oxime, — .     Pseudo  compounds, — . 

Nitro  Phenols  629 

Mono-nitro  phenol, — .    Tri-nitro  phenol,  Picric  acid, — .    Dyestuff, — .    Picrate 
explosives, — . 

Amino  Phenols  631 

Molecular    rearrangement    of    hydroxyl    amines, — .  Photographic   reducing 

agents, — .     Rhodinal,  Amidol,  Reducin,  Metol, — .  Ethers, — .    Acid  amide 

derivatives, — .      Phenetidine, — .      Phenacetine, — .  Dyes, — .      Azo  phenols, 
etc.,—. 

QUINONES  635 

Quinone, — .    Ketone  or  per-oxide, — .    Oximes, — .    Benzo-quinone, — .    Ortho- 
quinone,— . 

DERIVATIVES  OF  QUINONES  639 

Chloranil, — .     Chloranilic  acid, — .     Quinone  oximes, — . 

B.  AROMATIC  ALCOHOLS  641 

MONO-HYDROXY  COMPOUNDS  641 

Primary,  secondary,   tertiary,—.     Saturated  and  unsaturated,—.     Grignard 
synthesis,—.     Benzyl  alcohol,—.    Homologues, — .     Cinnamic  alcohol, — . 

POLY-HYDROXY  COMPOUNDS  645 

Aromatic    glycols— .    Phenol    alcohols,—.     Salicylic    alcohol,—.     Coniferyl 
alcohol, — . 

Thio-phenols  and  Aromatic  Mercaptans  646 


CONTENTS  XXXV 

PAGE 

VIII.  AROMATIC  ALDEHYDES  AND  KETONES        647 

Synthesis  from  alcohols, — .  From  halogen  substitution  products, — .  From 
hydrocarbons, — .  From  acids, — .  Reactions, — .  Polymerization, — .  Oxida- 
tion of  ketones, — .  Oximes  and  hydrazones, — .  Isomerism  of  benzaldoxime, — . 
Isomerism  of  ketoximes, — .  Beckmann  rearrangement, — . 

A.  ALDEHYDES  654 

Benzaldehyde  654 

Amygdalin, — . 

Higher  Aromatic  Aldehydes  656 

Cuminic  aldehyde, — .     Cinnamic  aldehyde, — . 

B.  KETONES  657 

Aceto  Phenone  657 

Benzo  Phenone  657 

SUBSTITUTED  ALDEHYDES  AND  KETONES  658 

HYDROXY  ALDEHYDES  AND  HYDROXY  KETONES  658 

Phenol  aldehydes  and  ketones, — . 

Hydroxy  Benzaldehydes  658 

Reimer-Tiemann  reaction, — .  Salicylic  aldehyde, — .  ^ara-Hydroxy  benz- 
aldehyde, — . 

Ethers,  Essential  Oils  66 1 

Anis  aldehyde, — .  Proto-catechuic  aldehyde, — .  Vanillin, — .  Relation  to 
eugenole,  etc., — .  Heliotropin  or  piperonal, — .  Alcohol-aldehydes  and 
-ketones, — . 

AMINO  KETONES  666 

ortho-Ammo  benzo  phenone, — .     Michler's  ketone, — .     Auramine, — . 

IX.  AROMATIC  ACIDS  669 

Character  and  type, — .  Methyl  to  carboxyl, — .  Oxidation  of  hydrocarbons, — . 
Mono-  and  poly-carboxy  acids, — .  Halogen  substitution  and  oxidation, — . 
Ring  carboxyl, — .  Side-chain  carboxyl, — .  Mixed  ring  and  side-chain 
carboxyl, — .  Synthesis  of  ring  carboxy  acids, — .  From  hydrocarbons, 
Friedel-Craft, — .  Friedel-Craft  reagent, — .  Gattermann  synthesis, — .  From 
aryl  halides,  Kekul6  synthesis, — .  Wurtz  synthesis, — .  From  sulphonic 
acids, — .  From  aryl  cyanides,  Acid  nitriles, — .  Nitriles  from  sulphonic 
acids  or  aryl  halides, — .  Nitriles  from  iso-thio-cyanates, — .  From  phenol 
esters, — .  From  acid  amides  and  anilides, — .  From  diazo  compounds, — . 
Ring  carboxy  acids  by  Grignard  reaction, — .  Synthesis  of  side-chain  carboxy 
acids, — .  From  aryl  halides, — .  From  aliphatic  acids, — .  With  malonic 
ester, — .  By  Grignard  reaction, — . 


XXXVi  CONTENTS 

PAGE 
Benzole  Acid  and  Derivatives  680 

Occurrence,—.  Syntheses,—.  Reduction,—.  Salts,—.  Benzene  from  ben- 
zoic  acid, — .  Benzophenone  from  benzoic  acid, — .  Esters, — .  Benzoyl 
chloride, — .  Benzoylation, — .  Benzoic  anhydride, — .  Benzoyl  amino  com- 
pounds,— .  Schotten-Baumann  reaction, — .  Benzamide, — .  Metal  salts, — . 
Benzoyl  phenyl  urea, — .  Hofmann  reaction, — .  Benzanilide, — .  Beckmann 
rearrangement, — .  Hippuric  acid, — . 

Toluic  Acids,  Xyloic  Acids,  Mesitylenic  Acid  687 

Phthalic  Acids  and  Derivatives  687 

Relation  to  xylene, — .  0r^0-Phthalic  acid, — .  Phthalic  anhydride, — . 
Phthalimide, — .  Phthalyl  chloride, — .  mela-  and  />ara-Phthalic  acids, — . 
Hydro-phthalic  acids, — . 

Uvitic  Acid,  Tri-mesitic  Acid,  Mellitic  Acid  695 

Phenyl  Acetic  Acid  696 

Hydro-cinnamic  Acid  and  Cinnamic  Acid  697 

Malonic  ester  synthesis  of  hydro-cinnamic  acid, — .  Perkin's  reaction, — . 
Isomerism, — .  Atropic  acid, — . 

Other  Unsaturated  Side-chain  Carboxy  Acids  700 

Phenyl  crotonic  acid, — .    Phenyl  vinyl  acetic  acid, — .    Phenyl  propiolic  acid, — . 

X.  SUBSTITUTED  AROMATIC  ACIDS  701 

RING  SUBSTITUTED  RING  CARBOXY  ACIDS  702 

Influence  of  carboxyl, — . 

HALOGEN  AROMATIC  ACIDS  704 

ortho-\Q&o  benzoic  acid, — . 

NITRO  AND  AMINO  AROMATIC  ACIDS  705 

Nitro  benzoic  acids, — .  Anthranilic  acid, — .  Relation  to  indigo, — .  Isatin, — . 
Anthranil, — .  Oxindole, — .  Synthesis  of  anthranilic  acid  and  indigo, — . 
From  phthalic  acid  and  naphthalene, — .  Hofmann  reaction, — .  Phenyl 
glycine  0^/w-carboxylic  acid,—.  Methyl  anthranilate,— .  Nitro  and  amino 
cinnamic  acids, — .  0r/A0-Amino  phenyl  propiolic  acid, — .  Phenyl  alanine, — . 
Azo,  hydrazo  and  diazo  acids, — . 

SULPHO  AROMATIC  ACIDS  712 

Sulpho  benzoic  acid, — .     Saccharin, — .     Synthesis, — . 

HYDROXY  AROMATIC  ACIDS  714 


CONTENTS  XXXV11 

PAGE 
PHENOL  RING  CARBOXY  ACIDS  714 

Salicylic  Acid  714 

Synthesis  from  sulpho  benzoic  acid, — .  From  amino  benzoic  acid, — .  From 
phenol, — .  Kolbe  synthesis, — .  From  phenol  by  carbon  tetrachloride, — . 
From  phenol  alcohols  and  phenol  aldehydes, — .  Salicin, — .  Oil  of  winter- 
green, — .  Methyl  salicylate, — .  Medicinal  properties  of  salicylic  acid, — . 
Salol, — .  Aspirin, — .  Anisic  acid, — . 

Poly-hydro xy  Mono-ring-carboxy  Acids  720 

Proto-catechuic  acid, — .  Vanillic  acid, — .  Gallic  acid, — .  Tannic  acids,- — . 
Gallo-tannic  acid, — .  Catechu-tannic  acid, — .  Querci-tannic  acid, — .  Caffe- 
tannic  acid, — .  Tannins, — .  Tanning, — .  Inks, — . 

PHENOL  SIDE-CHAIN  CARBOXY  ACIDS  726 

Tyrosine, — .  Hydroxy  cinnamic  acid, — .  Coumaric  and  coumarinic  acids, — . 
Coumarin,  new-mown  hay, — .  Perkin  synthesis, — . 

ALCOHOL  ACIDS  728 

Hydroxy-methyl  benzoic  acid, — .     Mandellic  acid, — . 

2.  DI-PHENYL  AND     RELATED  COMPOUNDS         730 

Di-phenyl  730 

Synthesis  from  benzene, — .  Di-nitro  di-phenyl, — .  Benzidine, — .  Di-anis- 
idine, — .  Di-phenic  acid, — . 

Di-phenyl  Methane  733 

Synthesis  by  Friedel-Craft  reaction, — .  Benzophenone, — .  Fluorene, — . 
Dyes, — .  Auramine,— . 

Tri-phenyl  Methane  735 

Synthesis, — . 

TRI-PHENYL  METHANE  DYES  736 

Methane  character, — .     Oxidation  products. — .     Benzene  character, — . 

Pararosaniline  738 

Tri-nitro  tri-phenyl  methane, — .  Tri-amino  tri-phenyl  methane, — .  Pararos- 
aniline leuco  base, — .  Tri-amino  tri-phenyl  carbinol,  carbinol  base, — . 
Pararosaniline  chloride, — .  Quinoid  structure  of  dyes, — .  Chromophore, — . 
Leuco  base, — .  Carbinol  base, — .  Colorless  hydrate  salt, — .  Colored  dye 
salt, — .  Preparation  of  pararosaniline, — . 

Rosaniline  743 

Historical,—.  Perkin,  Mauve,—.  Perkin  medal,—.  Fuchsin,— .  Magenta, 
— .  Hofmann — .  Fischer, — .  Caro,  Rosenstiehl,  SchorJemmer,  Hantzsch, 
Nietski, — .  Formaldehyde  and  phosgene  methods, — .  Synthetic  dyes, — . 


xxxviii  CONTENTS 

PAGE 

Malachite  Green  747 

Rosolic  Acid  748 

PHTHALEIN  DYES  75° 

Phenolphthalein  75° 

Preparation  from  phthalic  acid, —  Tri-phenyl  methane  derivative, — . 
Phthalo-phenone — .  Color  and  constitution  of  phenol  phthalein, —  Quinoid 
structure, — .  Dissociation  theory, — .  Pyronine  structure, — . 

Rhodamines  75° 

Fluorescein  759 
Uranine — . 

Eosine  761 

Tri-phenyl  Methyl  762 

Di-benzyl,  Stilbene,  Tolane  762 

Benzoin,  Benzil  763 

3.  CONDENSED  RING  COMPOUNDS  765 

NAPHTHALENE  AND  DERIVATIVES  765 

Naphthalene  765 

Coal  tar  source, — .  Constitution,- — .  Benzene  character, — .  Yields  ortho- 
phthalic  acid, — .  Synthesis  from  phenyl  butylene  bromide, — .  From  phenyl 
vinyl  acetic  acid, — .  From  tetracarboxy  ethane, — .  Two  benzene  rings, 
Erlenmeyer,  Graebe, — .  Chlor  naphthalenes,—.  Tetra-hydro  naphthyl- 
amines, — . 

DERIVATIVES  775 

Isomerism, — .  Mono-substitution  products,  alpha-  and  beta, — .  Di-sub- 
stitution  products, — . 

Halogen  D  erivativ  es  777 

Substitution  products, — .     Addition  products, — . 

Nitro  Naphthalenes  778 

Naphthylamines  779 

Synthesis  from  naphthols, — .  0^a-Naphthylamine, — .  foto-Naphthyl- 
amine, — .  Relation  to  dyes, — .  Diazotization, — .  Reagen-t  for  nitrites  in 
water, — .  Hydrated  naphthylamines, — . 

Naphthalene  Sulphonic  Acids  782 

Naphthols  782 

Synthesis  from  naphthalene  sulphonic  acids,—.     From  naphthylamines,—. 
Dyes,  Orange  II,—.     Betol,  Salol,— . 


CONTENTS  XXXIX 

PAGE 
MIXED  SUBSTITUTION  PRODUCTS  OF  NAPHTHALENE         784 

Nitro  Naphthols  785 

Martius'  yellow, — .     Naphthol  yellow  S, — . 

Naphthylamine  Sulphonic  Acids  and  Naphthol  Sulphonic  Acids  786 

Naphthionic  acid, — .     Eikonogen, — . 

Azo  Dyes  from  Naphthalene  786 

Congo  red, — .  Benzo  purpurin, — .  Naphthol  blue  black, — .  Fast  red  B, — . 
Bordeaux  B, — . 

Naphthoquinones  790 

Naphthoic  and  Naphthalic  Acids  791 

ANTHRACENE  AND  DERIVATIVES  792 

Anthracene  792 

Condensed  benzene  rings, — .  Synthesis  from  tetra-brom  ethane, — .  From 
ortho-benzyl  toluene, — .  From  ortho-brom  benzyl  bromide, — .  From  phenyl 
ortho-tolyl  ketone, — .  Three  benzene  nucleii, — . 

Anthraquinone  795 

Synthesis  from  phthalic  acid, — .  Character  of  center  nucleus, — .  Isomer- 
ism, — . 

Alizarin  .800 

Turkey  red, — .  Synthesis  by  Graebe  and  Liebermann,— .  Reduction  to 
anthracene, — .  i-2-Di-hydroxy  anthraquinone,  Baeyer  and  Caro, — .  Com- 
mercial synthesis, — .  Industrial  importance,  — . 

PHENANTHRENE  AND  DERIVATIVES  806 

Phenanthrene  806 

Synthesis  from  stilbene  and  from  di-tolyl, — .  From  ortho-ammo  alpha- 
phenyl  cinnamic  acid, — .  From  ortho-brom  benzyl  bromide, — .  Phenanthra- 
quinone  and  di-phenic  acid, — .  Retene  and  pyrene, — . 

4.  HYDROGENATED  BENZENE  COMPOUNDS          Sn 
NAPHTHENES  8n 

Hydro  benzenes, — .     Quinone  and  phloroglucinol, — . 

CYCLO  HEXANOLS  813 

Chinitol,  Quercitol,  Inositol  814 

Phytin,-^, 

TERPENES  814 

HYDROCARBONS  815 

Terpenes  and  hemi-terpenes, — .     Olefine  and  cyclic  terpenes, — . 


xl  CONTENTS 

PAGE 
I.  OLEFINE  TERPENES  815 

Isoprene  815 

Citrene  and  Derivatives  815 
Geraniol, — .     Citral, — .     lonone, — . 

II.  CYCLIC  TERPENES  816 

A.  MONO-CYCLIC  TERPENES  817 
Cymene, — . 

Menthane  Group  818 

Menthene  Group  8 1 8 

Isomerism, — . 

Mentha-di-ene  Group  819 

Limonenes,  Terpinenes,  etc.  819 

^-/-Limonene, — .    Di-pentene, — .    J-Limonene, — .    Citrene, — .    /-Limonene, — . 
Terpinenes,—.     Phellandrene, — .     Sylvestrene, — . 

B.  DI-CYCLIC  TERPENES  821 

Carane,  Thuj  ene  822 

Pinane,  Pinene  823 

Pinene  hydrochloride, — .     imitation  camphor, — .     Synthetic  camphor,' — . 

Camphane,  Camphene,  Bornylene  823 

OXIDATION  DERIVATIVES  OR  CAMPHORS  825 

MONO-CYCLIC  DERIVATIVES  825 

Menthol,  Menthone,  etc.  825 

From    menthane, — .       Carvo-menthol,— .       Carvomenthone, — .      Terpin, — . 
Terpin  hydrate, — .     Cineol, — . 

Terpineol,  etc.  828 

Derivatives    of    menthene, — .     Di-hydro    carveol, — .     Di-hydro    carvone,- — . 
Position  of  double  bond, — .     Pulegone, — . 

Carvone  83 1 

Mentha-di-ene  ketones, — .     Scheme  of  relationships, — . 

DI-CYCLIC  DERIVATIVES  836 

Bornylene,  Borneol,  Camphor  836 

Thujone, — .    Fenchone, — .     Constitution  of  camphor — .     Kompa's  synthesis 
of  camphoric  acid, — .     Synthesis  of  camphor, — .     Natural  camphor, — . 

Turpentine  Industry  840 

Rosin,  Colophony, — . 


CONTENTS  Xll 

PAGE 

ESSENTIAL  OILS  AND  PERFUMES  841 

Esters, — .  Aldehydes, — .  Ethers, — .  Olefine  terpenes, — .  Cyclic 
terpenes, — . 

TABLE  XX.  ESSENTIAL  OILS  843 

Rubber,  Caoutchouc  844 

Source, — .  Coagulation, — .  Properties, — .  Manufacture, — .  Vulcaniza- 
tion,— .  Constitution, — .  Synthesis, — .  Isoprene, — . 

SECTION  II.  HETERO-CYCLIC  COMPOUNDS    8si 

Open-chain  derivatives, — . 

A.  FIVE  MEMBERED  RINGS  852 

Furfuran  and  Furfural  852 

Pyro-mucic  acid, — .     Furfuryl  alcohol, — . 

Thiophen  854 

Pyrrole  855 

Pyrrolidine  856 
Proline, — . 

Pyrrazole,  Pyrrazoline,  Pyrrazolone  857 
Antipyrine, — . 

B.  SIX  MEMBERED  RINGS  858 

Pyridine  858 

Derivatives, — .     Hydroxy  pyridines, — .     Carboxylic  acids, — . 

Piperidine  860 

Pyridine  Homologues  860 

Picolines, — .  Lutidines, — .  Collidines, — .  Conine, — .  Synthesis  of  colli- 
dine, — . 

C.  CONDENSED  HETERO-CYCLIC  COMPOUNDS       862 

SIX  MEMBERED  COMPOUNDS  863 

Quinoline  863 

Baeyer  and  Drewsen's  synthesis, — .  Skraup's  synthesis, — .  Derivatives,—. 
Hydroxy  quinolines, — .  Carbo-styril, — .  Carboxylic  acids, — .  Cinchoninic 
acid, — .  Quinolinic  acid, — .  Hydrogenated  quinolines, — .  Kairoline, — .  Iso- 
quinoline, — . 


xlii  CONTENTS 

PAGE 
FIVE  MEMBERED  COMPOUNDS  867 

Indole,  Oxindole,  Di-oxindole,  Isatin,  Indoxyl  868 

Skatole,  Tryptophane  872 

Indigo  873 

Aniline, — .  Anthranilic  acid, — .  Isatin,  Indole,  etc., — .  Isatin  chloride, — . 
Synthesis  of  indigo, — .  From  di-phenyl  di-acetylene, — .  Baeyer  and  Emmer- 
ling,  Indole  from  ortho-mtro  cinnamic  acid, — .  Engler  and  Emmerling,  Indigo 
from  ortho-mtio  acetophenone, — .  From  ortho-nitre  phenyl  acetic  acid, — . 
Benzaldehyde, — .  ortho-Nitro  cinnamic  acid, — .  ortho-Nitro  propiolic  acid, — . 
Baeyer  and  Drewsen,  ortho-mtra  benzaldehyde, — .  '  Heumann's  synthesis, — . 
Phenyl  glycine  <?r^0-carboxylic  acid, — .  Naphthalene  to  anthranilic  acid, — . 
Industrial  indigo, — .  Natural  indigo, — . 

D.  ALKALOIDS  886 

ALKALOIDS  RELATED  TO  PYRIDINE  887 

Conine  887 

Piperine  888 

Nicotine  888 

ALKALOIDS  RELATED  TO  QU1NOLINE  888 

Quinine  and  Cinchonine  889 

Strychnine  and  Brucine  891 

Morphine,  Codeine,  Narcotine,  Papaverine  892 

Opium, — .     Physiological  action, — .     Heroine, — . 

DI-HETERO-CYCLIC  ALKALOIDS  894 

Hyoscyamine,  Atropine,  Tropine  894 

Cocaine  896 

Synthetic  Anesthetics  897 

a^/ra-Cocaine, — .  alpha-Eucame, — .  beta-Eucame, — .  Stovaine, — .  Aly- 
pine, — .  Orthoform, — .  Anesthesine, — .  Novocaine, — . 

PURINE  ALKALOIDS  902 

Synthesis  of  xanthine, — . 

Caffeine,  Theobromine,  Theophylline  905 

Xanthine,  Hypoxanthine,  Adenine,  Guanine  905 


CONTENTS  Xliii 

PAGE 

PTOMAINES  906 

Putrescine,  Cadaverine  907 

.Ergot  base,  Hordenine  908 

Lecithin,  Choline,  Neurine  908 

Muscarine,  Betaine  910 

Conclusion  911 

BOOKS  OF  REFERENCE  912 

APPENDIX  915 

Separation,    Purification,    Identification,    Analysis    and  Determination    of 

Molecular  Weight  of  Organic  Compounds.  915 


ORGANIC  CHEMISTRY 

PART  I 
A-CYCLIC    COMPOUNDS— ALIPHATIC    SERIES 

INTRODUCTION 

Organic  and  Inorganic  Compounds. — The  distinction  between 
organic  and  inorganic  compounds  and  the  classification  of  all  substances 
into  these  two  groups,  with  the  division  of  the  science  of  Chemistry 
into  the  two  fields  of  Organic  Chemistry  and  Inorganic  Chemistry,  rests 
upon  the  fact  that  organic  compounds  were  originally  found  in  nature 
associated  with,  and  as  the  result  of,  organized  or  living  matter,  i.e., 
plants  or  animals.  In  this  origin  they  were  in  distinct  contrast  to  other 
known  compounds  which  were  termed  inorganic  because  they  were 
obtained  from  non-living  matter,  i.e.,  the  rocks,  minerals  and  salts  of  the 
earth's  crust.  It  was  supposed  that  the  vital  process  of  living  organisms 
was  essential  to  the  formation  of  the  organic  compounds,  and  as  many  of 
these  seemed  to  be  of  an  entirely  different  nature  from  that  of  the 
common  inorganic  compounds  they  were  naturally  believed  to  be  of 
a  distinct  order  and  even  unrelated  to  the  ordinary  chemical  laws  as 
worked  out  in  connection  with  the  study  of  inorganic  substances. 

In  1828  Wohler  made  urea  (p.  429)  a  product  of  animal  life,  from 
ammonium  cyanate  which  is  a  substance  that  may  be  prepared  in  the 
laboratory  from  non-living  or  inorganic  material.  This  epoch-making 
discovery,  while  in  no  sense  so  wonderful  or  so  striking  as  many  synthe- 
ses since  accomplished,  marked  the  beginning  of  the  realization  of  the 
fact,  that  organic  compounds,  while  produced  in  nature  through  the 
action  of  living  organisms,  were,  nevertheless,  of  the  same  order  and 
followed  the  same  chemical  laws  as  the  compounds,  which  were  non- 
living or  inorganic.  It  soon  became  an  established  fact  that  many 
organic  compounds  could  be  made  in  the  laboratory  by  reactions  of  the 
same  nature  as  those  used  in  making  the  inorganic. 


2  ORGANIC    CHEMISTRY 

Furthermore,  as  time  went  on,  new  organic  compounds  were  made 
which  had  never  been  found  associated  with  living  things.  Some  of 
these  were  later  found  in  nature  while  many  have  remained  solely  the 
product  of  laboratory  reactions.  Thus  a  large  number  of  compounds 
became  known  as  organic  not  because  they  were  produced  by  living 
organisms  but  because  they  were  directly  related  to  other  compounds 
originally  so  produced.  The  classification  of  compounds  as  organic 
or  inorganic  rests,  therefore,  upon  their  relationship  to  other  compounds 
and  not  upon  the  circumstances  of  their  natural  occurrence.  A  com- 
pound is  organic  then  because  it  is  related  to  certain  other  compounds 
and  it  was  found  that  those  which  were  thus  related  and  grouped  to- 
gether were  all  compounds  of  carbon  or,  to  be  more  definite,  were 
compounds  of  hydrogen  and  carbon  or  derivatives  of  these.  The 
phrase,  hydrogen  compounds  of  carbon  and  their  derivatives,  becomes 
thus  a  truer  description  of  what  we  now  mean  by  organic  compounds 
than  their  connection  with  organized  or  living  matter. 

All  this  does  not  mean  that  the  vital  property  of  organisms  is  simply 
a  laboratory  process  or  that  having  made  a  compound  known  to  be 
produced  in  living  plants  or  animals  we  have  produced  or  can  produce 
the  living  organism  itself. 


A.  SIMPLER  SATURATED  COMPOUNDS 

I.  HYDROCARBONS  OF  THE  METHANE  SERIES.— PARAFFINS 

GENERAL 

The  study  of  Organic  Chemistry  begins  with  the  simplest  compound 
of  the  two  elements  carbon  and  hydrogen  and,  as  we  proceed  and  the 
subject  develops,  we  shall  find  that  this  and  similar  compounds  are  the 
mother  substances  from  which  all  of  the  vast  number  of  organic  com- 
pounds may  be  derived.  We  can  realize  at  once  therefore  the  extreme 
importance  of  these  fundamental  compounds  and  also,  the  significance 
of  the  definition  given  in  the  Introduction  that  organic  chemistry  is 
the  chemistry  of  the  hydrogen  compounds  of  carbon  and  their  derivatives. 
The  magnitude  of  the  number  of  organic  compounds  will  be  realized 
when  we  state  that  according  to  the  most  recent  enumeration  in  Rich- 
ter's  "Lexikon  der  Kohlensto/verbindungen,"  3rd.  ed.  and  in  the  "Reg- 
ister der  Kohlenstoffverbindungen,"  1911-1914,  there  are  more  than 
200,000  known  compounds. 

Hydrocarbons. — These  hydrogen  compounds  of  carbon  are  known  as 
hydrocarbons,  a  name  the  significance  of  which  is  readily  understood 
as  indicating  the  two  elements  of  which  they  are  composed.  It  is  well 
at  the  outset  to  guard  against  a  confusion,  which  sometimes  arises  in 
the  mind  of  the  beginner,  with  another  group  of  compounds  having  a 
similar  name  but  which  are  of  a  distinctly  different  character,  viz., 
carbohydrate  s.  As  the  name  indicates  the  carbohydrates  were  supposed 
to  be  compounds  of  carbon  and  water.  Their  true  character  will  be 
understood  later  together  with  the  reasons  for  supposing  that  they  con- 
tained carbon  and  water.  At  present  it  is  sufficient  simply  to  guard 
against  confusing  hydrocarbons,  hydrogen-carbon  compounds  and  car- 
bohydrates, carbon-water  compounds. 

Paraffins. — Carbon  and  hydrogen  do  not  unite  directly  under 
ordinary  laboratory  conditions  but  in  certain  natural  substances  com- 
pounds of  the  two  elements  are  present.  Similar  compounds  of  the 
two  elements  may  also  be  formed  by  the  decomposition  of  complex  sub- 
stances containing  other  elements  than  carbon  and  hydrogen.  The 
hydrocarbons  so  found  or  formed  are  usually  very  stable  compounds  and 

3 


4  ORGANIC   CHEMISTRY 

many  of  them  show  little  affinity  toward  other  substances  especially 
the  ordinary  laboratory  reagents  such  as  alkalies,  acids,  oxidizing  and  re- 
ducing agents,  etc.  '  This  statement  applies  especially  to  the  group  of 
hydrocarbons  with  which  we  begin  our  study  and  which,  on  account  of 
their  stability  and  inactivity  toward  other  substances,  have  been  given 
the  name  paraffins,  from  the  two  Latin  words  parum,  too  little  and 
affinis,  akin. 

The  common  substance  which  we  know  as  paraffin  is  composed  of 
such  hydrocarbon  compounds. 

Methane.     CH4 

Marsh  Gas. — The  simplest  hydrocarbon  of  this  paraffin  series 
and  therefore  the  one  with  which  our  study  will  begin  is  known  by  the 
chemical  name  of  methane,  the  series  being  also  known  as  the  methane 
series.  It  is  found  in  nature  and  has  a  common  name  often  used,  viz., 
marsh  gas.  As  this  name  indicates  it  occurs  as  a  gaseous  emanation 
arising  from  marshes  where  it  has  been  formed  by  the  slow  decomposi- 
tion of  vegetable  matter  without  the  presence  of  oxygen  or  air.  In 
winter  air  bubbles  which  form  in  the  ice  may  sometimes  be  shown  to 
contain  methane  and  when  opened  give  off  a  gas  which  will  burn.  This 
will  be  found  to  occur  especially  on  ponds  which  contain  large  amounts 
of  decaying  vegetation. 

Fire  Damp. — Analogous  to  this  non-oxi"dizing  decomposition  of 
vegetation  in  marshes  and  ponds  is  the -slow  geologic  decomposition  of 
plant  life  by  which  coal  has  been  formed.  Here  also  methane  was 
produced  and  is  now  found  shut  up  in  pockets  and  crevices  in  the  coal 
strata.  The  gas  obtained  from  such  pockets  may  consist  of  as  much  as 
80  to  90  per  cent  methane,  the  remainder  being  mostly  nitrogen.  When 
the  coal  is  mined  this  gas  is  liberated  in  the  mine  and  there  becomes 
mixed  with  air.  When  the  methane  gas  and  air  become  thus  mixed  in 
about  the  proportion  of  one  volume  of  methane  to  two  volumes  of  oxygen 
(ten  volumes  of  air)  there  is  produced  an  exceedingly  explosive  mixture 
which  may  become  ignited  by  a  spark  or  a  free  candle  flame,  and  which 
in  this  manner  is  the  cause  of  disastrous  mine  explosions.  This 
explosive  mixture  of  methane  and  air  is  called  fire  damp. 

Coal  Gas,  Natural  Gas,  Petroleum. — From  its  natural  formation 
and  occurrence  as  marsh  gas  and  as  fire  damp  it  is  not  surprising  to 
find  that  methane  occurs  also  as  a  constituent  of  three  related  sub- 


HYDROCARBONS    OF   THE   METHANE   SERIES  5 

stances,  viz.,  coal  gas,  natural  gas  and  petroleum.  The  two  natural 
products,  natural  gas  and  petroleum,  are  in  fact  complex  mixtures  of 
hydrocarbons  in  whose  formation  various  reactions  have  had  to  do. 
The  discussion  of  the  probable  origin  of  these  products  and  of  their 
industrial  importance  will  be  considered  at  length  later.  Methane  is 
also  found  as  a  constituent  of  intestinal  gases  where  it  is  produced  by 
the  fermentation  of  carbohydrate  food.  After  a  meal  of  legumes  the 
intestinal  gases  may  contain  as  much  as  56  per  cent  of  methane. 

Physical  Properties. — Methane  is  a  colorless  and  odorless  gas.  It 
is  lighter  than  air  and  when  pure  may  be  readily  liquefied.  The  weight 
of  one  liter  of  methane  is  o.7i46g.  and  22.4  litres  (gram  molecular  vol- 
ume) weigh  16.00  g.  It  is,  therefore,  7.952  times  as  heavy  as  hydrogen 
which,  as  may  be  recalled,  weighs  0.08987  g.  per  liter.  The  density 
of  methane  is  then  7.952,  and  its  molecular  mass  is  16.00. 

Chemical  Properties. — The  chemical  properties  of  methane  are 
characteristic  of  this  entire  group  of  hydrocarbons,  which  on  account 
of  these  properties  are  known  by  the  general  name  of  paraffins.  To- 
ward ordinary  reagents  such  as  sulphuric  acid,  nitric  acid,  chromic 
acid,  alkalies  and  salts,  methane  is  practically  inactive.  It  burns  in 
air  or  oxygen  with  a  more  or  less  luminous  flame.  By  passing  the  prod- 
ucts of  combustion  over  calcium  chloride  and  into  lime  water  it  may 
readily  be  shown  that  water  and  carbon  dioxide  have  been  formed, 
thus  showing  the  presence  in  methane  of  the  two  elements  hydrogen 
and  carbon.  If  a  cool  surface  is  placed  in  the  burning  jet  of  methane 
gas  a  black  deposit  of  carbon  will  be  obtained.  When  mixed  with  oxy- 
gen in  the  proportion  of  one  volume  of  methane  to  two  volumes  of  oxygen, 
or  with  air  in  the  proportion  to  yield  this  same  ratio  of  methane  and 
oxygen,  i.e.,  one  volume  of  methane  to  ten  volumes  of  air,  an  explosive 
mixture  is  formed,  yielding,  in  case  pure  oxygen  is  used,  only  carbon 
dioxide  and  water. 

Formula,  CH4. — The  analysis  of  methane  shows  that  it  contains 
approximately  75  per  cent  carbon  and  25  per  cent  hydrogen.  This  to- 
gether with  the  facts  in  regard  to  its  density  and  molecular  weight  give 
us  the  data  for  the  calculation  of  the  composition  formula  for  the  com- 
pound which  has  been  established  as  CH4,  i.e.,  one  atom  of  carbon  and 
four  atoms  of  hydrogen.  The  reaction  with  oxygen  may  be  written 
therefore  as: 

CH4    +    2O2  -*        CO2  +  2H2O 

Methane 


6  ORGANIC    CHEMISTRY 

Synthesis  from  the  Elements. — We  may  now  consider  methods  for 
the  formation  of  methane  and  in  particular  its  synthesis  from  the 
elements.  Though,  as  has  been  stated,  hydrogen  and  carbon  do  not 
unite  directly  under  ordinary  laboratory  conditions,  they  do  unite^ 
directly  when  a  mixture  of  the  two  elements  is  heated  to  1200°, 
methane  being  the  product. 

C2  +  4H2(i200°) >          2CH4 

Methane 

Berthelot's  Synthesis. — When  carbon  disulphide  and  hydrogen  sul- 
phide are  passed  together  over  heated  copper  or  iron,  methane  is  formed 
according  to  the  f ollowing  reaction  : 

CS2  +  2H2S  +  4Cu >        CH4     +      4CuS 

Methane 

This  is  known  as  Berthelot's  Synthesis.  As  carbon  disulphide  may 
be  made  by  heating  together  carbon  and  sulphur,  and  hydrogen  sul- 
phide is  the  product  of  the  direct  union  of  sulphur  and  hydrogen,  we 
may  consider  this  as  an  indirect  synthesis  of  methane  from  the  elements. 
A  similar  reaction  occurs  when  carbon  disulphide  and  steam  are  passed 
over  heated  copper. 

CS2  +  2H20  +  4Cu        >        CH4   +    2CuS  +   2CuO 

Methane 

Methane  from  Carbides. — Another  method  of  preparation  is  of 
interest  and  importance  because  of  its  connection  with  theories  as  to 
the  formation  of  methane  and  other  hydrocarbons  in  petroleum.  With 
some  metals  carbon  forms  compounds  which  are  very  stable  at  high 
temperatures,  and  which  have  been  artificially  produced  in  the  electric 
furnace  (about  35oo°C.)  by  Moissan.  These  metallic  carbon  com- 
pounds, known  as  carbides,  are,  most  of  them,  easily  decomposed  by 
water  at  ordinary  temperatures,  and  when  so  decomposed  they  yield 
various  members  of  the  hydrocarbon  group  of  compounds.  A  familiar 
example  of  this  class  of  reactions  is  the  one  by  which  acetylene  gas  is 
made  by  the  action  of  water  on  calcium  carbide.  The  carbide  of 
aluminium  decomposes  with  water  and  yields  methane  according  to 
the  following  reaction: 

A14C3     +     i2H20 >         3CH4   +   4A1(OH)8 

Aluminium  Methane 

carbide 

Laboratory  Preparation  of  Methane.— As  it  is  not  practicable  to 
obtain  naturally  occurring  methane  for  study,  we  must  resort  to  labora- 


HYDROCARBONS    OF    THE   METHANE    SERIES  7 

tory  methods  of  preparation.  Two  general  methods  may  be  used  for 
making  it.  The  first  is  the  synthesis  from  simpler  compounds  or  from 
the  elements  as  just  mentioned  and  the  second  is  by  the  decomposition 
of  more  complex  substances.  While  the  first  method  might  be  con- 
sidered as  the  logical  one  with  which  to  begin,  it  is  not  a  practical 
one,  and  we,  therefore,  obtain  methane  by  decomposing  a  more  com- 
plex compound. 

Methane  from  Sodium  Acetate.— Acetic  acid,  as  we  shall  understand 
before  we  have  proceeded  far  in  our  study,  is  a  compound  related  to 
methane.  When  the  sodium  salt  of  this  acid,  i.e.,  sodium  acetate,  is 
heated  it  loses  carbon  dioxide,  CO2,  and  methane  is  produced.  In 
practice  this  heating  is  carried  out  in  the  presence  of  an  .alkali,  e.g., 
calcium  or  sodium  hydroxide,  which  absorbs  the  carbon  dioxide,  and  in 
this  way  assists  in  the  reaction.  In  order  that  we  may  not  be  troubled 
by  the  presence  of  water,  dry  materials  are  used,  the  sodium  acetate 
being  fused  to  obtain  it  free  of  water.  When  this  dry  sodium  acetate 
is  heated  with  a  mixture  of  sodium  and  calcium  hydroxides,  known  as 
soda-lime,  a  gas  is  produced  which  may  be  collected  over  water.  The 
gas  so  made  is  methane  and  is  identical  with  that  found  naturally  as 
marsh  gas  and  as  a  constituent  of  fire  damp,  natural  gas,  coal  gas  and 
petroleum. 

Reaction  with  Halogens. — We  have  referred  to  the  inactivity  of 
methane  and  the  hydrocarbons  in  general.  With  only  one  group  of 
substances  does  methane  show  any  readiness  to  react.  The  members 
of  the  halogen  group  of  elements,  especially  chlorine,  react  with  methane 
in  an  exceedingly  characteristic  way,  and  it  is  by  a  study  of  these  re- 
actions that  light  is  thrown  upon  the  real  nature  of  this  compound,  and 
the  whole  group  of  hydrocarbons  that  are  similar  to  it,  leading  event- 
ually to  an  understanding  of  the  entire  subject  of  organic  chemistry. 

When  a  mixture  of  methane  gas  and  chlorine  gas  is  ignited,  or  when 
an  ignited  jet  of  methane  is  burned  in  a  jar  of  chlorine,  action  takes 
place  and  one  of  the  products  is  always  hydrochloric  acid  gas.  When  the 
action  takes  place  suddenly  as  in  the  case  of  an  explosion  of  a  mixture 
of  the  two  gases  in  the  proportion  of  one  volume  of  methane  to  two 
volumes  of  chlorine,  the  only  other  product  is  carbon.  This  reaction  may 
be  easily  carried  out  in  the  laboratory  and  may  be  represented  as  follows: 

CH4    +    2C12        >        4HC1    +    C 

Methane 


8  ORGANIC    CHEMISTRY 

The  reaction  is  simply  one  of  metathesis  by  which  the  chlorine  unites 
with  the  hydrogen  and  leaves  the  carbon,  and  it  shows  us  nothing  more 
than  did  the  combustion  in  oxygen,  viz.,  that  methane  is  a  compound  of 
carbon  and  hydrogen. 

If,  however,  instead  of  by  a  sudden  reaction  the  chlorine  acts  upon 
the  methane  slowly,  as  will  be  the  case  when  a  mixture  of  the  two  gases 
in  the  proportion  of  four  volumes  of  methane  to  ten  volumes  of  chlorine 
(4.CH4:  ioC!2),  is  allowed  to  stand  in  diffused  sunlight,  the  products 
of  the  reaction  are  wholly  different.  Instead  of  the  chlorine  taking  all 
of  the  hydrogen  and  leaving  only  carbon  it  takes  the  hydrogen  little  by 
little.  It  is  found,  in  fact,  that  the  hydrogen  is  removed,  one  atom  at  a 
time,  and  that  as  each  hydrogen  atom  is  taken  by  the  chlorine  to  form 
hydrochloric  acid  an  atom  of  chlorine  enters  the  methane  molecule  in  place 
of  the  hydrogen  removed.  This  reaction  goes  on  step  by  step  until  all 
of  the  hydrogen  is  removed  from  the  methane  molecule  and  an  equal 
number  of  chlorine  atoms  have  combined  with  the  methane  carbon 
atom.  Thus  we  may  represent  the  steps  in  the  reaction  as  follows: 
4  CH4  +  4  C12 >  4  CH3C1  +  4  HC1 

Methane 

3  CH3C1  +     3  C12  ~>        3  CH,C12  +  3  HC1 

2  CH2C12  +     2  C12  -i          2  CHC13  +  2  HC1 

i  CHC13  +     i  C12  r-»  i  CC14  +  i  HC1 

Total   4  CH4  +  10  C12  — »  CH3C1  +  CH2C12  + 

CHC13  +  CC14  +  10  HC1 

When  the  reaction  takes  place  as  described  the  product  is  a  mixture  of 
hydrochloric  acid  gas  and  all  four  of  these  new  compounds. 

Chlor  methanes. — What  now  are  these  four  new  compounds  and 
how  do  they  throw  light  upon  the  nature  of  methane?  In  the  first 
place,  all  four  of  them  have  been  isolated  and  their  composition  and 
formulas  determined.  They  are  called  chlor-methanes  and  to  distin- 
guish them  the  number  of  chlorine  atoms  in  the  molecule  is  indicated  by 
a  numerical  prefix,  i.e., 

CH3C1,   Mono-chlor  methane 
CH2C12,  Di-chlor  methane 
CHC13,    Tri-chlor  methane 
CC14,       Tetra-chlor  methane 

Two  of  these  compounds  are  well  known  substances,  viz.,  tri-chlor 
methane,  which  is  the  valuable  anaesthetic  chloroform  and  tetra- 


HYDROCARBONS    OF    THE    METHANE    SERIES  9 

chlor  methane,  which  is  known  as  carbon  tetra-chloride,  and  is  a  sol- 
vent of  fats,  etc.     These  will  be  considered  in  detail  later  on. 

Substitution. — A  reaction  of  the  kind  we  have  just  been  considering 
in  which  an  element  is  removed  from  a  compound  and  another  element 
is  put  in  its  place  is  known  as  a  reaction  of  substitution,  and  the  compound 
formed  is  called  a  substitution  product.  In  the  cases  cited  chlorine 
is  substituted  for  hydrogen.  The  replaced  element  is  always  the  hydro- 
gen of  a  hydrocarbon  or  of  the  hydrocarbon  portion  of  a  complex  com- 
pound, but  the  substituting  element  may  be  any  monovalent  element  or 
a  monovalent  group  of  elements.  A  bivalent  or  trivalent  element  or 
group  of  elements  may  be  similarly  substituted  for  two  or  three  hydro- 
gen atoms  at  once.  The  substitution  products  of  any  compound,  therefore, 
are  compounds  derived  from  it  by  replacing  one  or  more  hydrogen  atoms 
by  an  equivalent  number  of  elements  or  gro.ups  of  elements.  Among  the 
most  important  substitution  products  are  those  in  which  hydrogen  is 
substituted  by  (a)  the  halogens  (chlorine,  bromine,  iodine),  (b)  the 
hydroxyl  group,  OH,  (c)  the  amino  group,  NHz  (the  monovalent  residue 
of  ammonia,  NHS),  (d)  the  cyanogen  group,  CN. 

Theory  of  Substitution. — In  these  substitution  products  it  has  been 
shown  that  the  substituting  element  or  group  not  only  takes  the  same 
place  as  the  hydrogen  which  it  has  replaced,  but  in  a  certain  respect  acts 
like  the  hydrogen  in  the  resulting  compound,  so  that  oftentimes  the 
substitution  products  possess  a  similar  character  to  the  original  com- 
pound. This  may  seem  strange  at  the  outset  when  we  consider  the 
difference  in  character  between  hydrogen  and  the  examples  of  substi- 
tuting groups  we  have  mentioned,  viz.,  halogens,  hydroxyl,  cyanogen  and 
the  ammonia  residue.  Objection  on  this  ground  was  especially  strong 
at  the  time  the  idea  of  substitution,  particularly  as  applied  to  organic 
compounds,  was  first  suggested  by  the  French  chemist,  Dumas,  in 
1834.  The  theory  was  strongly  opposed  by  Berzelius,  who  had  pre- 
viously advanced  the  electro-chemical  theory  according  to  which  every 
element  or  group  possessed  definite  electrical  properties,  some  being 
positive  and  others  negative.  As  hydrogen  was  positive  and  chlorine 
negative  he  held  that  it  was  impossible  for  one  to  take  the  place  of  the 
other  in  a  compound.  So  many  facts  were  brought  forth,  however, 
which  confirmed  the  theory  that  it  became  generally  accepted,  and 
has  been  one  of  the  most  helpful  of  theories  in  connection  with  the 
development  of  our  ideas  as  to  the  real  nature  of  organic  compounds. 


10  ORGANIC    CHEMISTRY 

We  shall  speak  of  this  again  and  bring  out  some  of  the  strongest  facts 
which  support  the  theory  when  we  take  up  the  chlorine  substitution 
products  of  acetic  acid. 

Structure  of  Methane. — We  shall  now  consider  some  additional 
facts  in  regard  to  these  chlorine  substitution  products  of  methane, 
i.e.,  the  chlor  methanes,  and  see  how  they  help  us  to  form  an  idea  as  to 
the  structure  of  the  methane  molecule.  By  the  structure  or  constitu- 
tion of  a  compound  we  mean  the  relation  of  each  element  or  group  of 
elements  to  every  other  element  in  the  molecule.  In  other  words,  the  way 
the  compound  is  built  up  or  its  structure.  In  its  widest  significance 
the  structure  of  a  compound,  i.e.,  the  structure  of  its  molecule,  must  have 
to  do  with  the  geometrical  relations  of  the  constituent  elements  or 
groups  in  space,  and  this  will  be  our  final  consideration  of  the  matter 
when  we  come  later  to  treat  of  what  is  termed  the  stereo-chemistry  of 
the  molecule  of  organic  compounds.  For  the  present  our  consideration 
of  the  structure  of  organic  compounds  will  have  to  do  only  with  the 
order  in  which  the  different  elements  or  groups  are  joined  together  to  build 
up  the  molecule.  Furthermore,  it  should  be  emphasized  that  our  ideas 
of  the  structure  of  a  compound  are  not  simply  notions  as  to  how  the 
elements  may  be  joined  together,  but.  are  based  upon  definite  known 
reactions,  and  are  but  the  direct  interpretation  of  these  known  reactions. 

Tetra-valence  of  Carbon. — At  the  beginning  of  our  study  of  the 
real  nature  of  the  compounds  of  carbon  we  make  an  assumption  which, 
though  it  is  upheld  by  a  majority  of  the  facts,  is  still  only  an  assumption. 
In  organic  compounds  the  -valence  of  carbon  is  four  and  is  practically 
invariable.1  In  inorganic  chemistry,  when  an  element  unites  with 
another  element  in  more  than  one  proportion,  we  explain  it  by  saying 
that  the  valence  of  one  of  the  elements  has  changed.  For  example, 
carbon  forms  tw*o  different  oxides,  one  of  which  corresponds  to  the  for- 
mula CO2,  in  which  we  say  the  valence  of  carbon  is  four.  In  the  other 
the  formula  is  CO,  and  we  say  the  valence  of  carbon  here  is  two.  Now 
there  is  known  a  hydrocarbon  which  has  only  one-half  as  much  hydro- 
gen in  proportion  to  the  carbon  as  methane,  its  formula  being  C2H4. 
In  this  compound,  as  we  shall  see  later  on,  and  in  almost  all  similar 
cases  in  organic  chemistry,  the  facts  of  composition  are  explained,  not 

1  Recent  investigations  and  theories  that  have  to  do  with  exceptions  to  the  un- 
varying tetra-valence  of  carbon  will  not  be  considered  in  this  book  as  they  pertain 
to  a  more  advanced  study"  than  is  contemplated. 


HYDROCARBONS  OF  THE  METHANE  SERIES          II 

by  saying  that  the  valence  of  carbon  has  changed  to  two,  but  that  the 
valence  of  the  carbon  is  not  wholly  satisfied. 

Methane  a  Saturated  Compound. — Certain  facts  in  connection  with 
the  relation  of  chlorine  to  methane  indicate  that  the  valence  of  carbon 
in  organic  compounds  does  not  go  above  four,  i.e.,  that  four  is  at  least 
its  maximum  valence.  When  chlorine  reacts  with  methane  it  is  always 
by  an  act  of  substitution.  Whenever  a  halogen  atom  enters  the  me- 
thane molecule  it  does  so  only  when  an  atom  of  hydrogen  has  been  given 
up.  Under  no  known  conditions  does  methane  form  compounds  con- 
taining one  or  more  halogen  atoms  in  addition  to  the  four  hydrogen 
atoms  already  held  by  the  carbon.  We  express  this  fact  by  saying 
that  the  carbon  atom  in  methane  is  saturated  by  the  four  hydrogen 
atoms.  Methane,  then,  is  termed  a  saturated  compound.  We  have 
spoken  of  the  fact  that  the  hydrocarbons  are  called  paraffins  because 
of  their  lack  of  affinity  for  other  substances.  Strictly  speaking  it  is 
only  those  hydrocarbons  which,  like  methane,  are  saturated  to  which 
the  name  paraffin  applies.  Methane  is  the  simplest  member  of  the 
saturated  hydrocarbons  or  paraffins.  The  first  idea  then  as  to  the 
structure  of  methane  which  the  facts  indicate  is,  that  in  it  the  carbon 
atom  is  saturated,  or  in  other  words,  four  hydrogen  atoms  fully  satisfy 
the  valence  of  carbon  in  methane. 

Methane  a  Symmetrical  Compound. — A  second  idea  as  to  the  struc- 
ture of  methane  is  gained  likewise  from  a  study  of  the  chlorine  or  other 
halogen  substitution  products.  The  following  fact  has  been  estab- 
lished, viz.,  that  there  is  known  only  one  compound  each  corresponding  to. 
the  formulas  for  mono-chlor  methane,  di-chlor  methane  and  tri-chlor 
methane.  When  mono-chlor  methane  is  formed  one  atom  of  chlorine 
is  substituted  for  one  atom  of  hydrogen  in  the  original  methane  mole- 
cule, and  the  chlorine  takes  the  same  position  as  the  substituted  hydrogen. 
If  now  the  four  hydrogen  atoms  in  methane  are  in  different  relations 
to  the  carbon  atom  we  should  at  least  expect  that  sometimes  one 
hydrogen  and  sometimes  another  would  be  substituted  by  the  chlorine. 
If  this  were  so  then  we  should  expect  to  have  two  or  more  mono-chlor 
methanes  differing  from  each  other  in  some  way.  The  fact  is  that  al- 
though mono-chlor  methane  has  been  made  many  times,  and  by  dif- 
ferent reactions,  yet  there  has  never  been  obtained  a  second  compound 
corresponding  to  the  formula  CH3C1. 

If  we  represent  methane  as  C  H1  H2  H3  H4  in  which  we  have 


12  ORGANIC    CHEMISTRY 

numbered  the  different  hydrogen  atoms,  then  in  case  H1  H2  H3  and  H4 
afe  all  different  we  should  have 

C  Cl  H  H  H 

C  H  Cl  H  H 

C  H  H  Cl  H 

C  H  H  H  Cl 

as  the  formuals  for  four  different  mono-chlor  methanes.  The  fact 
that  only  one  mono-chlor  methane  is  known  goes  to  show  that  H1  H2  H3 
H4  are  all  alike  and  bear  the  same  relation  to  the  carbon  atom  in  the 
methane  molecule.  In  addition  to  this  indirect  proof  it  has  been 
shown  that  each  of  the  four  hydrogen  atoms  in  methane  may  be  re- 
placed one  and  only  one  at  a  time  by  one  chlorine  atom,  and  the 
four  resulting  mono-chlor  methanes  are  identical.  In  methane,  there- 
fore, the  four  hydrogen  atoms  are  alike  in  their  relation  to  the  carbon 
atom,  or  in  other  words  the  methane  molecule  is  symmetrical. 

Structural  or  Constitutional  Formula. — To  represent  a  compound 
whose  formula  is  CH4  in  a  way  that  will  indicate  the  two  facts  just 
discussed,  viz.,  saturation  of  the  carbon  atom,  and  symmetrical  arrange- 
ment of  the  four  hydrogen  atoms,  the  following  graphic  formula  is  used : 

H 

I 
H— C— H 

H 

Methane 

This  means  that  methane  is  CH4,  a  saturated,  symmetrical  compound, 
in  which  carbon  is  tetra-valent,  and  all  of  the  hydrogens  are  alike.  It 
should  be  emphasized  again  that  such  a  formula,  which  we  call  a 
structural  or  constitutional  formula,  does  not  represent  the  arrangement 
of  the  atoms  in  space,  but  is  simply  a  plane  representation  of  the  most 
important  facts  in  regard  to  methane  as  shown  by  definite  reactions. 
The  structural  formulas  for  methane  and  the  four  chlor  methanes  are 
then  as  follows: 

H  H  H  Cl  Cl 

I  I  I  I  I 

H— C— H      H— C— Cl      H— C— Cl      H— C— Cl      Cl— C— Cl 

I  I  I  I  I 

H  H  Cl  Cl  Cl 

Methane  Mono-chlor  Di-chlor  Tri-chlor  Tetra-chlor 

methane  methane  methane  methane 


HYDROCARBONS    OF    THE    METHANE    SERIES  13 

It  is  very  important  to  grasp  at  the  beginning  the  full  significance  and 
likewise  the  limitations  of  these  structural  formulas.  To  repeat;  the 
formula  for  mono-chlor  methane,  viz., 

H  H 

H — C — Cl  means  that  it  is  derived  from  methane,  H — C — H 

H  H 

by  substituting  one  chlorine  atom  for  one  hydrogen  atom.  The  four 
hydrogen  atoms  being  alike  it  makes  no  difference  in  which  position  we 
place  the  chlorine.  Also,  carbon  is  tetra-valent,  and  methane  and 
mono-chlor  methane  are  saturated  compounds  in  which  each  of  the 
four  hydrogen  atoms  or  each  of  the  hydrogen  atoms  and  the  chlorine 
atom  are  joined  directly  to  the  carbon  atom.  The  formula  is  a  plane 
representation  of  these  fads,  and  indicates  nothing  as  to  space  relations. 
When  chlorine  is  substituted  for  hydrogen  in  methane  and  mono- 
chlor  methane  is  obtained,  we  may  assume  as  probable  that  one  chlo- 
rine atom  first  removes  hydrogen  from  the  methane  molecule,  and  then 
a  second  chlorine  atom  unites  with  the  residue  of  methane.  When 
one  hydrogen  is  removed  from  methane  we  have  left  the  residue 
(CH3  — ),  i.e.,  CH4  may  be  written  CH3  — H.  In  mono-chlor  methane, 
then,  the  chlorine  may  be  considered  as  united  to  the  residue  (CH3  — ) 
which  as  a  group  possesses  the  one  valence  of  the  carbon  left  unsatis- 
fied by  the  one  lost  hydrogen.  By  our  structural  formulas  we  may 
represent  the  relations  between  methane  and  mono-chlor  methane  as 

H  H 

I  I 

H— C— H  or  CH3— H  H— C— Cl  or  CH3— Cl 

I  I 

-H-          Methane  "      Mono-chloi -methane 

As  in  mono-chlor  methane  chlorine  is  thus  represented  as  joined  to  the 
group  (CH3  — ),  so  in  all  mono-substitution  products  of  methane  a 
monovalent  element  or  group  is  joined  to  the  monovalent  group  (CH3— ). 
A  general  formula,  therefore,  for  all  mono-substituted  methanes  may  be 
written,  CH3— X;  X  being  any  mono-valent  element  or  group. 

Radical. — It  has  been  found  that  there  is  a  large  series  of  compounds 
all  of  which  contain  this  group  (CH3  — )  and  all  of  which  are  derived 


I4  ORGANIC    CHEMISTRY 

from  or  related  to  methane.  Furthermore,  not  only  this  group,  but 
many  other  groups  act  in  a  similar  way,  forming  different  series  of 
compounds,  each  series  containing  a  common  group.  A  group  of  ele- 
ments thus  running  unchanged  through  a  series  of  compounds  has  been 
called  a  radical. 

The  theory  of  radicals  was  held  for  some  time  in  a  general  and  rather 
indefinite  way,  both  as  applied  to  inorganic  and  organic  compounds, 
before  the  year  1832.  But  in  this  year  two  chemists  whose  names  are 
always  associated,  and  both  of  whom  brought  about  great  advances  in 
organic  chemistry,  viz.,  Liebig  and  Wb'hler,  published  a  joint  investi- 
gation (m"The  Radical  of  Benzole  Acid."  In  this  investigation  they 
showed  that  a  group  of  elements  (C7H5O-),  according  to  our  present 
atomic  weights,  was  present  in  a  series  of  some  nine  compounds,  which 
were  readily  transformable  into  each  other.  As  a  result  of  this  classical 
investigation,  and  others  which  followed,  the  idea  of  an  organic  radical 
became  more  and  more  firmly  established.  A  radical  came  to  be 
considered  as  a  group  of  several  elements,  in  a  compound,  joined 
together  more  securely  than  the  rest  of  the  compound,  and  which 
remains  unchanged  as  a  constituent  of  a  series  of  related  compounds. 
In  itself  it  may  be  replaced  by  other  elements  or  groups,  and  is  also 
possible  of  undergoing  substitution,  thereby,  however,  becoming  a  new 
radical.  Hardly  any  theory  that  has  been  advanced  has  had  a  more 
powerful  and  fruitful  effect  than  this  theory  of  radicals,  and  it  has  been 
one  of  the  great  ideas  which  has  enabled  chemists  to  understand  the 
character  of  organic  compounds  and  to  change  a  miscellaneous  group  of 
unrelated  compounds  into  a  definite  system  of  wonderfully  related  ones. 
Liebig  himself  termed  organic  chemistry  the  "chemistry  oj  the  compound 
radical."  In  any  series  of  compounds,  and  every  compound  was  soon 
shown  to  belong  to  a  more  or  less  extended  series,  the  constant  unit 
which  was  the  basis  of  relationship  was  the  radical.  The  other  part  of 
the  compound  was  alterable  at  will  through  ordinary  laboratory  re- 
actions, so  that  the  transformation  of  one  compound  into  others  was 
readily  brought  about  and  relationships  thus  established.  Compounds 
took  their  names  from  those  of  the  radicals  present  in  them. 

Methyl.— The  radical  (CH3-)  is  known  as  methyl  and  the  com- 
pounds containing  it  are  termed  methyl  compounds.  Similar  names 
have  been  given  to  all  radicals  by  taking  a  part  of  the  word  used  as  the 
name  of  the  compound  from  which  the  radical  is  derived,  and  adding  the 


HYDROCARBONS    OF    THE    METHANE    SERIES  15 

termination  yl.  In  almost  all  cases  the  radical  is  not  known  as  such 
and  has  not  been  isolated.  R  is  used  to  denote  any  radical,  usually  one 
derived  from  a  hydrocarbon. 

Methyl  Halides. — The  mono-halogen  substitution  products  of 
methane,  of  which  we  have  been  speaking,  are  known  by  this  new  sys- 
tem of  names  as  methyl  compounds  so  that  we  have  the  two  sets  of 
names  for  the  same  substances,  both  of  which  are  correct  and  either  of 
which  expresses  the  relationship  to  methane. 

Mono-chlor  methane  CH3C1  Methyl  chloride 
Mono-brom  methane  CH3Br  Methyl  bromide 
Mono-iodo  methane  CH3I  Methyl  iodide 

The  general  name  being: 

Mono-halogen  methanes  Methyl  halides 

These  two  ideas  or  theories  of  substitution  and  of  radicals  and  the  facts 
in  regard  to  methyl  compounds  enable  us  to  understand  the  relationship 
between  methane  and  the  hydrocarbon  next  higher  to  it  in  the  series. 

Ethane     C2H6 

This  compound  is  similar  to  methane  in  many  ways.  It  is  a  gas, 
slightly  heavier  than  air,  having  a  density  of  15.0.  It  is  colorless  and 
odorless  and  burns  with  a  flame  somewhat  more  luminous  than  that  of 
methane.  It  is  found  in  nature  in  sources  similar  to  those  of  methane, 
as  in  natural  gas  and  in  petroleum.  Like  methane  it  is  chemically 
inactive  and  a  hydrocarbon  of  the  paraffin  series. 

Ethane  a  Saturated  Compound. — Like  methane,  ethane  is  unable 
to  take  up  chlorine  or  any  other  element  without  at  the  same  time  losing 
hydrogen  and  forming  a  substitution  product.  This  is  the  character 
we  term  saturation  and  in  methane  we  say  that  four  hydrogens  or  any 
four  monovalent  elements  are  all  that  carbon  with  its  tetra-valence  can 
hold.  Now  in  ethane  these  same  facts  are  true.  Analysis,  however, 
shows  ethane  to  have  the  composition  C2H6  and,  according  to  our  usual 
manner  of  regarding  union  between  atoms,  if  carbon  remains  tetra- 
valent,  as  we  have  previously  stated,  only  six  of  a  total  of  eight  bonds  or 
valences  are  satisfied.  How,  then,  have  these  facts  been  brought  into 
harmony? 

Synthesis  of  Ethane. — By  a  consideration  of  the  synthetic  prepara- 
tion of  ethane  from  methane  we  are  able  to  understand  its  structure  in 


1 6  ORGANIC    CHEMISTRY 

accordance  with  our  ideas  of  the  tetra-valence  of  carbon,  and  with  the 
fact  that  it  acts  as  a  saturated  compound.  When  mono-iodo  methane, 
which  we  have  also  called  methyl  iodide,  and  which  name  will  usually 
be  used,  is  treated  with  zinc  or  sodium,  ethane  is  formed,  two  molecules 
of  methyl  iodide  yielding  one  of  ethane.  In  this  reaction  the  iodine  is 
taken  by  the  zinc  or  sodium  and  we  may  write  the  reactions: 

2CH3I     +     Zn >     C2H6  +  ZnI2    or 

Methyl  iodide  Ethane 

2CH3I     +    2Na       — >     C2H6  +  2NaI 

Methyl  iodide  Ethane 

These  two  reactions  are  known  by  the  names  of  the  men  who  discovered 
them.  The  first  one,  with  zinc,  is  known  as  the  Frankland  Reaction 
and  will  be  spoken  of  again  (page  76).  The  second,  with  sodium, 
is  known  as  the  Wurtz  Reaction. 

The  radical  methyl  which,  as  we  stated,  does  not  exist  free,  is  rep- 
resented as  having  a  valence  of  one. 

H 

CH3—  or  H— C— 

I 
H 

Methyl  radical 

One  of  the  four  bonds  of  the  carbon  is  left  free.  In  methane  this  free 
bond  is  satisfied  by  another  hydrogen  atom;  in  methyl  chloride  or  iodide 
by  one  of  chlorine  or  iodine,  making  in  each  case  a  saturated  compound. 
When,  therefore,  two  molecules  of  methyl  iodide  each  lose  their  iodine 
to  zinc  or  sodium  we  have  left  the  two  methyl  radicals  with  this  fourth 
valence  of  each  carbon  unsatisfied.  These  two  free  valencies  satisfy 
each  other,  and  we  have  the  two  methyl  radicals  united,  just  as  we  believe 
two  free  atoms  unite  to  form  a  molecule.  We  may  write  the  reaction 
then: 

H  H  H    H 

I  I  I 

H— C— (I  +  Zn  +  I  )— C— H  -  ->  H—  C— C— H  +  ZnI2 

I  I  II 

H  H  H     H 

Methyl  iodide  Ethane 


HYDROCARBONS    OF    THE    METHANE    SERIES  1 7 

Ethane  may  be  considered  then  as  di-methyl,  or  as  methyl  methane,  i.e., 
methane  in  which  a  methyl  radical  (CH3-)  has  been  substituted  for  one 
hydrogen  atom.  In  it  three  of  the  valencies  of  each  carbon  atom  are 
satisfied  by  hydrogen  atoms  while  the  fourth  valencies  of  the  two  carbon 
atoms  mutually  satisfy  each  other.  The  two  carbon  atoms  thus  be- 
come directly  linked  together.  In  such  a  compound  both  of  the  carbon 
atoms  have  all  four  of  their  valencies  satisfied,  and  the  compound  is, 
therefore,  saturated.  This  formula  then  agrees  both  with  the  fact  that 
ethane  acts  as  a  saturated  compound  and  with  the  theory  that  carbon  is 
tetra-valent  and,  furthermore,  it  is  the  logical  explanation  of  the  reaction 
by  which  it  is  formed  from  methyl  iodide. 

The  next  question  which  arises  in  regard  to  ethane  is ;  is  ethane  like 
methane  in  being  symmetrical,  i.e.,  are  all  of  the  hydrogen  atoms  alike 
in  their  relation  to  the  carbon  atoms  and  to  each  other?  The  same 
kind  of  facts  which  established  this  point  in  regard  to  methane  are 
also  true  of  ethane,  viz.,  only  one  mono-chlor  ethane  is  known.  We  thus 
conclude  that  all  six  hydrogen  atoms  in  ethane  are  alike,  and  no  matter 
which  one  is  substituted  by  chlorine  the  product  is  always  the  same. 
We  may  write  the  structural  formula  for  mono-chlor  ethane  then : 

H    H 

I      I 
C2H5— Cl,  CH3— CH2— Cl     or    H— C— C— Cl 

I      I 
H    H 

Mono-chlor  ethane 

The  general  formulas  for  mono-substitution  products  of  ethane  are: 

H    H 

I 
C2H5— X,          CH3— CH2— X     or     H— C— C— X 

I       I 
H    H 

Mono-substitution  products  of  ethane 

The  radical  of  ethane  is  analogous  to  methyl  and  is  known  as  ethyl. 

H    H 

(C2H5)-  (CH3— CH2)-     or    H— C— C- 

H    H 

Ethyl  radical 


1 8  ORGANIC  CHEMISTRY 

One  other  fact  should  be  noticed  here.  We  see  that  ethane,  C2H6, 
differs  in  composition  from  methane,  CH4,  in  having  one  carbon  and 
two  hydrogens  more,  i.e.,  by  (CH2).  This  is  clearly  understood  when 
we  remember  tha  in  making  ethane  from  methane  we  have  taken  away 
one  hydrogen  and  put  in  its  place  (CH3)  or  we  have  really  added  (CH2). 

Propane,  Butane,  Pentane,  Hexane  and  the  Higher  Saturated  Hydrocarbons 

We  have  now  laid  the  foundation  for  considering  the  other  hydro- 
carbons which  are  similar  to  methane  and  ethane  and  for  understanding 
an  interesting  relationship  which  makes  of  them  a  family  or  series.  At 
the  present  time  about  fifty  hydrocarbons  are  known  which  resemble 
methane  and  ethane  in  being  saturated,  stable,  inactive  compounds,  and 
to  which  the  name  paraffin  strictly  applies.  Some  of  these  hydro- 
carbons with  their  empirical  formulas  and  a  few  of  their  physical  con- 
stants are  given  in  the  following  table: 

Several  striking  things  will  be  noticed  in  regard  to  the  hydro- 
carbons given  in  this  table  as  to  their  (a)  physical  properties,  (b)  com- 
position, (c)  structure  or  constitution.  It  will  be  noted  that  the 
compounds  are  arranged  in  the  order  of  their  carbon  content. 

Physical  Properties. — On  examining  the  physical  properties  of  the 
hydrocarbons  given  it  will  be  seen  that  these  properties  vary  in  a  more 
or  less  progressive  and  constant  manner,  usually  increasing  as  we  go  up 
the  series.  The  four  lower  members  from  methane  to  butane  are  gases 
at  ordinary  temperatures,  the  next  thirteen  are  liquids  below  25°,  while 
the  remainder  are  solids.  This  can  be  seen  more  clearly  by  examining 
the  three  physical  constants  given,  in  each  of  which,  especially  the 
melting  point  and  boiling  point,  there  is  a  more  or  less  uniform  increase 
from  the  first  member  to  the  highest. 

Composition  and  Constitution. — A  similar  constant  progressive 
change  is  seen  in  the  composition.  Each  compound  differs  from  the 
one  immediately  preceding  it  by  the  constant  amount  CHs.  As  will 
be  recalled  this  was  spoken  of  in  the  case  of  ethane  as  being  the  differ- 
ence in  composition  between  it  and  methane.  It  was  shown  then  that 
this  is  in  accord  with  its  synthesis  from  methyl  iodide  and  sodium, 
ethane  being  methyl  methane  (p.  16). 

Not  only,  however,  does  this  synthesis  make  plain  to  us  the  con- 
stitution of  ethane  and  its  relation  to  methane,  but  the  reaction  is  a 
general  one  for  the  synthesis  of  hydrocarbons  and  for  establishing  their 


HYDROCARBONS    OF   THE    METHANE    SERIES 


TABLE  I. — HOMOLOGOUS  SERIES  OF  SATURATED  HYDROCARBONS  (PARAFFINS) 
General  Formula  CnH2n+2 


Name 

No.  of 
isomers 
known 

Empirical 
formula 

Melting 
point 
(M.P.) 

Boiling 
point 
(B.P.) 

Specific 
gravity 
(Sp.  Gr.) 

Methane  
Ethane                  

CH4 
C2H6 

-i  86° 

At  760  mm. 
-152° 
-  00° 

0.415  (-164°) 

Propane                         .  . 

C3H8 

-  37° 

Butanes 

2 

Normal  butane 

+     i° 

o  60  (o°) 

2  -methyl  propane  
Pentanes           

•z 

C4Hio 
C5Hi2 

-   11.15° 

Normal  pentane  

CbHl2 

30° 

0.6337  (15°) 

2  -methyl  butane 

31° 

0  6271  (re0} 

2-2-di-methyl  propane 
Hexanes       

t 

C6H12 

-   20° 

9° 

Normal  hexane 

C6H14 

60° 

0   66^4.  ClS0) 

3  -methyl  pentane  
2-methyl  pentane  
2-3-di-methyl  butane.  . 
2-2-di-methyl  butane 

•• 

CeHi4 
C6H14 
C6H14 
C6HU 

64° 
62° 
58° 
40.6° 

0.6765   (20-5°) 

0.6766  (o°) 

0.6680(17.5°) 

0.6488  (20°) 

Normal  heptane  

e 

08.4° 

o.68s  (20°) 

Normal  octane.  .  . 

2 

C8Hi8 

125° 

O.  7O2  (20°) 

Normal  nonane  
Normal  decane  . 

3 
6 

C9H20 

-   5i° 
-   li° 

150° 

m° 

0.718(20°) 

O.  7?o  (20°) 

Normal  undecane  
Normal  dodecane  
Normal  tridecane  
Normal  tetradecane. 

i 
i 
i 
i 

CiiH24 
Ci2H2e 
CuH28 

-   26° 

-     12° 

-     6° 
+      4° 

195° 
214° 

234° 

252° 

0.774  (M.P.) 
0.773  (M.P.) 
0.775  (M.P.) 
o  775  (M  P) 

Normal  pentadecane  
Normal  hexadecane  
Normal  heptadecane  
Normal  octadecane  
Normal  nonadecane  

Normal  eicosane  
Normal  heneicosane  
Normal  docosane  

i 

2 
I 
I 
I 

I 
I 

I 

CisH32 
CieHs* 
Cr/Hsc 
CisHas 
C19H40 

C20H42 
C2iH44 
C22H46 

10° 

18° 

22° 
28° 
32° 

37° 
40° 
44° 

270° 
287° 
303° 
317° 
330° 

At  15  mm. 
205° 

215° 
224° 

0.776  (M.P.) 
0.775  (M.P.) 
0.777  (M.P.) 
0.777  (M.P.) 
0.777  (M.P.) 

0.778  (M.P.) 
0.778  (M.P.) 
0.778  (M.P.) 

Normal  tricosane  
Normal  tetracosane  
Normal  hexacosane  
Normal  heptacosane  
Normal  hentriacontane..  . 
Normal  dotriacontane.  .  .  . 
Normal  pentatriacontane. 
Normal  hexacontane  

I 
I 
I 
I 
I 

I 

I 

I 

C2sH48 

C24Hso 
C2eHs4 
C27H56 
C3iHe4 
Ca2H66 

CssH72 

CeoHi22 

48° 
5i° 
44° 
60° 
68° 
70° 
75° 

101° 

234° 
243° 

270° 

302° 

310° 
33i° 

0.779  (M.P.) 
0.779  (M.P.) 

0.780  (M.P.) 
0.781  (M.P.) 
0.781  (M.P.) 
0.782  (M.P.) 

20  ORGANIC  CHEMISTRY 

constitution.     By  means  of  it  the  methyl  radical  may  be  linked  to 
any  other  radical,  a  new  hydrocarbon  thereby  resulting. 

R  _  (i  +  Na2  +  I)  -  CH3  R  -  CH3  +  2NaI 

Propane  and  Butane. — In  this  way  propane,  C3H8,  has  been  made 
from  ethyl  iodide,  methyl  iodide  and  sodium  and  it  must  therefore 
be  methyl  ethane.  Also  butane,  C4H10,  similarly  made  from  propyl 
iodide,  methyl  iodide  and  sodium,  is  methyl  propane.  The  reactions 
are  as  follows:1 

C2H5—  (I  +  Na2  +  I)— CH3    — -»     C2H5— CH3  +  2  Nal 

Ethyl  iodide  Methyl  iodide  Propane 

Methyl  ethane 

C3Hr-(I  +  Na2  +  T)— CH3    >     C3H7— CH3  +'2  Nal 

Propyl  iodide  Methyl  iodide  Butane 

Methyl  propane 

This  general  method  of  synthesis  has  been  applied  to  each  member 
of  the  methane  series  with  the  result  that  each  hydrocarbon  has  been 
proven  to  be  the  methyl  substitution  product  of  another  hydrocarbon  con- 
taining one  less  carbon  atom.  We  have  then  for  the  successive  members 
of  the  series  a  continually  elongating  chain  of  carbon  groups,  each 
group  being  a  residue  of  methane.  For  the  first  six  members  the  for- 
mulas are  as  follows: 

Methane,  CH3— H  Butane,      CH3— CH2— CH2— CH3 

(Methyl  (Methyl  propane) 

hydride) 

Ethane,     CH3— CH3  Pentane,    CH3— CH2— CH2— CH2— CH3 

(Methyl  methane)  (Methyl  butane) 

Propane,  CH3— CH2— CH3  Hexane,     CH3— CH2— CH2— 

(Methyl  ethane)  CH2— CH2— CH3 

(Methyl  pentane) 

Etc. 

A-cyclic  or  Open  Chain  Compounds. — Such  compounds,  because 
their  structure  is  that  of  a  chain  of  carbon  groups,  the  ends  of  which 
chain  do  not  unite  to  form  a  ring,  are  known  as  open  chain  or  a-cyclic 
compounds  in  distinction  from  closed  chain  or  cyclic  compounds  which 
we  shall  meet  with  in  the  second  part  of  our  study.  Their  structure 
explains  also  the  general  formula  for  the  series  as  given  at  the  top  of 
the  table,  viz.,  CnH2n+2.  Each  carbon  atom  excepting  the  two  end 

1  In  these  two  reactions  propane  and  butane  are  not  the  only  products,  other 
hydrocarbons  being  also  formed.     See  synthesis  of  butane  and  hexane  (p.  24  et  seq.). 


HYDROCARBONS    OF    THE    METHANE    SERIES  21 

ones,  is  linked  to  two  hydrogen  atoms.  The  two  end  carbon  atoms 
each  having  three  hydrogens  makes  the  total  number  of  hydrogen  atoms 
two  more  than  twice  the  carbon  atoms,  i.e.,  if  n  equals  the  number  of 
carbon  atoms  2n  -\-  2  will  equal  the  number  of  hydrogen  atoms. 
Therefore,  any  hydrocarbon  of  this  series  will  have  the  formula 

C,(H2n+2. 

Homologous  Series. — A  series  of  compounds,  the  members  of  which 
differ  in  composition  by  a  constant  amount,  and  whose  physical  con- 
stants change  uniformly,  constitute  what  has  been  termed  an  homolo- 
gous series.  This  particular  series  which  we  are  discussing  is  known 
as  the  homologous  series  of  the  saturated  or  paraffin  hydrocarbons,  which 
are  also  open  chain  or  a-cyclic  compounds,  the  general  formula  of  which 

is  C;iH2n+2- 

Names. — The  names  of  the  different  hydrocarbons  are  similar  and 
are  in  harmony  with  the  idea  of  an  homologous  series.  The  common 
termination  ane  is  given  to  all  and,  above  the  fourth  member,  a  Greek 
numerical  prefix  indicates  the  number  of  carbon  atoms  in  the  molecule. 
The  five-carbon  compound  is  pent-ane,  the  six  carbon  hex-ane,  etc. 
The  first  four  members  have  special  non-numerical  prefixes  as  meth- 
ane, eth-ane,  prop-ane  and  but-ane.  Similarly  the  radicals  of  each 
hydrocarbon  simply  take  the  termination  yl  in  place  of  ane,  thus, 
but-yl,  pent-yl,  hex-yl,  etc. 

.  Alkyl. — The  general  name  for  a  radical  of  this  series  is  alkyl.  A 
halogen  alkyl  or  alkyl  halide  is  thus  a  halogen  substitution  product  of 
any  paraffin  hydrocarbon,  or  it  is  composed  of  a  paraffin  or  alkyl 
radical  linked  to  a  halogen  atom.  The  general  formula  for  an  alkyl 
radical  is  (C»H2n+i). 

[/  Isomerism. — We  come  now  to  a  consideration  of  one  of  the  most 
*  interesting  phenomena  of  organic  chemistry,  viz.,  isomerism.  In 
speaking  of  ethane,  we  showed  how  the  fact  that  only  one  compound 
is  known  of  the  formula  C2H5 — Cl,  ethyl  chloride,  proves  that  in  ethane, 
as  in  methane,  all  of  the  hydrogen  atoms  are  alike  in  their  relation  to 
the  carbon  atoms.  When,  now,  we  study  the  third  hydrocarbon, 
propane,  we  find  a  new  fact  which  must  be  explained.  Mono-iodo 
propane,  which  is  the  mono-iodine  substitution  product  of  propane, 
usually  known  as  propyl  iodide,  has  by  analysis  the  formula  CaH? — I; 
but,  there  are  known  two  compounds  having  the  same  formula  but  dis- 
tinctly different  properties.  Both  of  these  compounds  are  prepared 


22  ORGANIC  CHEMISTRY 

from  propane  by  substituting  one  iodine  atom  for  one  hydrogen  atom  and 
each  of  them  is  therefore  propyl  iodide.     The  difference  in  the  physical 
properties  of  these  two  compounds  may  be  seen  from  the  following: 

B.P.     Sp.  Gr. 
Compound  A  ................................    102.5       I-?8 

Compound  B  ..................  ...............     89.0       1.74 

How  then  can  we  explain  the  existence  of  two  propyl  iodide  compounds 
of  the  same  molecular  formula  but  different  properties? 

The  structural  formula  for  propane,  based  upon  its  synthesis  from 
ethyl  iodide  and  methyl  iodide  in  the  presence  of  sodium,  is  as  shown  in 
the  following  reaction: 


CH3—  CHa—  (I  +  Na2  +  I)—  CH3         —  > 

Ethyl  iodide  Methyl  iodide 

H    H    H 

I       I       I 
CH3—  CH2—  CH3  or  H—  C—  C—  C—  H 

I       I       I 
H    H    H 

Propane 

There  are  eight  hydrogen  atoms  in  the  propane  molecule,  and  if 
propane  is  a  symmetrical  compound  and  all  of  the  hydrogen  atoms  are 
alike  in  relation  to  the  carbon  atoms  it  should  make  no  difference 
which  hydrogen  we  substitute  by  iodine.  The  fact  as  just  stated, 
however,  is  that  two  propyl  iodide  compounds  exist.  There  must  then 
be  two  hydrogen  atoms  in  the  propane  molecule,  each  of  which  is  in  a 
different  relation  to  the  carbon  atoms.  The  fact  again  is  that  only  two 
propyl  iodide  compounds  are  known;  therefore,  there  are  only  two 
hydrogen  atoms,  or  two  sets  of  hydrogen  atoms,  in  propane  that  are  dif- 
ferent. On  examination  of  the  structural  formula  for  propane,  viz., 

(6)  (7)  (8) 
H    H    H 

I  I 

(S)H—  C—  C—  C—  H(i)  or  CH3—  CH2—  CH3 

H    H    H 

(4)  (3)  .(2) 

Propane 

in  which  for  convenience  we  have  numbered  the  hydrogen  atoms,  we 
see  that  hydrogen  atoms  i,  2,  4,  5,  6,  8,  are  apparently  alike  and  are 


HYDROCARBONS    OF    THE   METHANE    SERIES  23 

each  linked  to  a  carbon  atom  which  is  linked  to  two  other  hydrogen 
atoms,  and  to  one  other  carbon  atom.  The  hydrogen  atoms  3  and  7, 
however,  are  linked  to  a  carbon  atom  which  is  linked  to  one  other  hydro- 
gen atom  and  to  two  other  carbon  atoms.  If  we  substitute  iodine  for 
one  of  the  hydrogen  atoms  i,  2,  4,  5,  6,  8,  we  will  have: 
H  H  H 

!    I 

H— C— C— C— I  or  CH3— CH2— CH2I 

I       I      I 
H    H    H 

Propyl  iodide,  A 

If  the  iodine  is  substituted  for  one  of  the  hydrogen  atoms,  3  or  7, 
we  have: 

H    H    H 

:— H  or  CH3— CHI— CH3 
H     I    H 

Propyl  iodide,  B 

If  the  hydrogen  atoms  2,  4,  5,  6  and  8  are  like  i  and  the  hydrogen 
atom  7  is  like  3,  then  only  these  two  different  compounds  would  be 
possible.  The  fact  that  two  and  only  two  propyl  iodides  are  known  leads 
to  the  conclusion  that  in  propane  there  are  two  sets  of  hydrogen  atoms 
and  only  two  sets,  and  that  substitution  of  iodine  for  any  one  of  the 
hydrogens  in  the  two  sets  will  yield  two  different  propyl  iodides.  Also, 
the  fact  that  two  different  mono-substituted  propanes  are  known  in 
each  of  the  classes  of  substitution  products,  viz.,  the  chlorine,  bromine, 
iodine,  methyl,  hydroxyl,  amino,  etc.,  strengthens  our  belief  in  this  idea. 

Structural  Isomerism. — The  phenomenon  of  the  existence  of  two 
or  more  compounds  possessing  the  same  composition  and  empirical 
formula  but  which  show  different  physical  and  chemical  properties  is 
known  as  isomerism,  and  the  compounds  themselves  are  called  isomeric 
compounds,  isomers  or  isomerides.  That  the  difference  is  in  the  struc- 
ture or  constitution  characterizes  them  further  as  structural  isomers 
and  the  phenomenon  as  structural  isomerism.  The  word  isomerism 
was  suggested  by  Berzelius  in  connection  with  Wb'hler's  synthesis  of 
urea  (p.  429). 

Isomeric  Hydrocarbons,  Butanes. — Having  explained  the  phenome- 
non of  isomerism  by  means  of  the  isomeric  propyl  iodides  we  shall 


24  ORGANIC  CHEMISTRY 

now  see  how  the  idea  is  applied  in  the  case  of  isomeric  hydrocarbons. 
We  have  shown  by  the  synthesis  of  the  hydrocarbons  (pp.  16-20)  that  as 
ethane  is  methyl  methane  and  propane  is  methyl  ethane  so  butane  is 
methyl  propane.  Methyl  propane,  being  a  methyl  substituted  propane 
is,  like  all  mono-substituted  propanes,  possible  of  existence  in  two  iso- 
meric forms  exactly  similar  in  their  structure  to  the  two  propyl  iodides, 
iodo  propanes.  We  should,  therefore,  expect  to  find  two  isomeric 
mono-methyl  propanes  or  butanes.  This  is  the  fact,  two  butanes  are 
known  possessing  the  same  composition  or  empirical  formula,  but  with 
different  properties  as  given  in  the  table  (p.  igj,  one  boiling  at  -f  i° 
and  the  other  at  —11.15°. 

Synthesis  of  the  Two  Butanes. — The  two  isomeric  propyl  iodides, 
by  means  of  the  Wurtz  and  Frankland  reactions,  yield  the  two  isomeric 
butanes,  the  constitution  of  which  must,  therefore,  be  as  shown  in  the 
following  reactions: 

HHH  H  HHHH 

I  III 

H— C— C— C— (i  +  2Na  +  I)— C— H  -  -»  H— C— C— C— C— H 

HHH  H  HHHH 

or 
CH3— CH2— CH2— (I  +  2Na  +  I)— CH3 >  CH3— CH2— CH2— CH3 

Propyl  iodide  Methyl  iodide  Butane,  Methyl  propane 

The  isomeric  propyl  iodide  yields  the  isomeric  butane 
HHH 

H— C— C— C— H  HHH 

I       M  III 

H    (I)    H  H-C-C-C-H 

+  I  I 

(Na)  — >  H  H 

+  | 

(I)  H— C— H 

H-C-H  H 

H 


HYDROCARBONS  OF  THE  METHANE  SERIES          25 

or 
CH3— CH— CH3 

I 
(I)  CH3— CH— CH3 

Na  CH3 

I  Isomeric  butane 

(I)— CH3 

Isomeric  propyl  iodide 

Pentanes  and  Hexanes. — In  exactly  the  same  way  in  which  we  have 
explained  the  isomerism  in  the  case  of  the  propyl  halides  and  butanes 
we  are  able  to  explain  that  of  the  pentanes  and  hexanes.  The  number 
of  possible  isomeric  hydrocarbons  naturally  increases  as  the  number  of 
carbon  atoms  increases.  Three  isomeric  hydrocarbons  of  the  formula 
CsH^  are  possible  and  three  are  known,  and  five  of  the  formula  C6Hi4, 
all  likewise  being  known. 

The  following  schematic  representation  of  the  relation  between  the 
hydrocarbons  from  methane  to  hexane  may  help  to  make  clear  the 
continually  increasing  number  of  isomers  possible. 

CHs  -  CHz— CHr- CH2I  (i) 
Butyl  iodide 

CHs— CHr- CH2I  CHs— GHz— CH2— CHs  (I) 

Propyl  iodide  Butane 

CHs—  CH— CHr- CHs  (2) 

I 

Isomeric  butyl  iodide 

CHs— H          CHs— CHs         CHs— CH2— CHs 
Methane  Ethane  Propane 

CHs— CH— CH2I    (3; 
I 

CHs 

Isomeric  butyl 
iodide 

CHs— CH— CHs  CHs— CH— CHs     (II) 
I 

I  CHs 

Isomeric  propyl  iodide  Isomeric  butane 

I  (4) 

I 

CHs— C— CHs 
1 

CHs 

Isomeric  butyl 
iodide 


26 


ORGANIC  CHEMISTRY 


CHr- GHz— CH2— CH*— CH2I      (i) 
Pentyl  iodide 

CHs— CH— CH2— CHr— CH3 
I 

I  (2) 

Isomeric  pentyl  iodide 

CHs— GHz— CH2— CHr— CHs       (I) 
Pentane 


CHy— CH2— CH2— GHz— CH2— CHs  (I) 
Hezane 

CHs— CH— CH2— CH2— CH3 
I 

CH3  (II) 

Isomeric  hexane 


CHs— GHz— CH— CHr- CHs 
I 

I  (3) 

Isomeric  pentyl  iodide 

CHi— CH— CHa— CH3 

!        I 

I  CHa  (4) 

Isomeric  pentyl  iodide 


CHs— CHr- CH— GHz— CH3 
I 

CH,  (III) 

Isomeric  hexane 

CHj— CHr- CH— CHz— CHs 
I 

CH3  (HI) 

Isomeric  hexane 


—  GHz— CH3 
I 

CH3 
Isomeric  pentane 


(ID 


CHs— C— GHz— CH3 

I 

CHs 
Isomeric  pentyl  iodide 

CHs— CH— CH— CHs 
I          I 
CH3   I 
Isomeric  pentyl  iodide 


(S) 


(6) 


CH3 
I 
CHs— C— CH 

! 

CH3 
Isomeric  hexane 


CH3 


CHs— CH— CH— CH3 
I  I 

CH»   CH3 
Isomeric  hexane 


(IV) 


(V) 


CHs— CH— CH2— CH3 


CH3  (II) 

Isomeric  pentane 

CHr— CH— GHz—  CH2I 
I 

CHs  (7) 

Isomeric  pentyl  iodide 

CH3 

I 
CHa— C— CHa 

I 

CH»  (HI) 

Isomeric  pentane 

CHa 

I 
CHy— C— CH2I 

I 

CH,  (8) 

Isomeric  pentyl  iodide 


CHs—CH— CH*—  CHz—  CH3 
I 

CH3 
Isomeric  hexane 


CH8 


CHa 
I 

-C— CH2— CH3 
I 


(II) 


CHa 
Isomeric  hexane 


(IV) 


HYDROCARBONS    OF   THE   METHANE    SERIES  27 

Normal  and  Iso  Compounds. — The  hydrocarbons  of  this  series 
have  been  spoken  of  as  belonging  to  the  general  class  of  a-cyclic  or 
open  chain  compounds.  By  examining  the  formulas  of  the  isomeric 
butanes,  pentanes  and  hexanes  on  the  preceding  page  it  will  be  seen 
that,  while  they  are  all  open  chain  compounds,  i.e.,  no  two  carbon  atoms 
are  linked  in  such  a  way  as  to  form  a  closed  ring,  yet  this  chain  is  more 
or  less  branched  in  all  cases  except  in  one  compound  of  each  isomeric 
group.  One  butane,  one  pentane  and  one  hexane  each  has  a  formula 
which  may  be  characterized  further  as  a  straight  open  chain  while  the 
others  are  all  branched  open  chains.  The  name  normal  has  been  applied 
to  these  straight  chain  formulas,  and  the  hydrocarbon  which  can  be 
shown  to  have  such  a  formula  is  known  as  the  normal  hydrocarbon. 
In  case  there  is  only  one  other  isomeric  compound,  as  with  the  butanes 
or  the  propyl  halides,  it  is  often  called  simply  the  isomeric  or,  abbre- 
viated, the  iso  compound.  Therefore 

CH3— CH2— CH2I,   Normal  propyl  iodide         CH3— CH— CH3,   Iso-propyl  iodide 

! 
i  . 

CH3— CH2— CH2— CH3,   Normal  butane      CH3— CH— CH3,  Iso-butane 

CH3 


The  question  now  arises,  how  may  we  determine  which  one  of  the 
various  formulas,  in  the  case  of  the  five  hexanes  for  instance,  is  to  be 
assigned  to  each  individual  compound  of  definite  physical  properties? 
To  which  one  of  the  butanes,  pentanes  and  hexanes  do  we  assign  the 
straight  chain  formula  or  the  name  normal?  In  the  case  of  the 
butanes  the  answer  and  the  reason  for  it  are  found  in  a  new  synthesis 
of  one  of  the  butanes.  We  have  given  one  synthesis  of  the  two  butanes, 
viz.,  from  propyl  iodide  and  methyl  iodide.  As  one  propyl  iodide 
yields  one  butane  and  the  other  yields  the  isomeric  butane,  we  know 
that  one  of  the  two  isomeric  butanes  must  have  the  straight  chain  or 
normal  formula.  But  we  do  not  know  whether  the  propyl  iodide  from 
which  the  butane  boiling  at  +  i°  is  prepared,  is  really  the  one  possess- 
ing the  normal  or  the  iso  formula.  Therefore,  it  will  be  seen  that  the 
relationship  between  the  isomeric  propyl  iodides  and  the  isomeric  bu- 


28  ORGANIC  CHEMISTRY 

tanes  explains  nothing  as  to  which  formula  belongs  to  which  compound 
until  we  have  some  proof  that  either  one  of  the  butanes  or  one  of  the 
propyl  iodides  is  in  fact  the  one  which  must  have  the  normal  formula. 
Now  butane  may  be  synthesized  in  another  similar  way.  If  ethyl 
iodide  alone  is  treated  with  sodium  or  zinc  we  obtain  only  one  butane 
as  the  product.  This  synthesis  proves  that  this  particular  butane  is 
di-ethyl  just  as  on  page  16  we  show  why  ethane  is  to  be  considered  as 
di-methyl. 

C2H5(I  +  2Na  +  I)C2H5  C2H5— C2H5 

or 
CH3— CH2(I  +  2Na  +  I)CH2— CH3       -4     CH3— CH2— CH2— CH3 

Ethy!  iodide  Butane,  Di-ethyl 

Now  the  only  way  in  which  two  ethyl  radicals  may  be  linked  to- 
gether is  as  a  straight  chain  compound,  and  therefore  the  butane  so 
made  must  be  the  one  with  the  straight  chain  formula,  and  the  one  which 
we  must  call  normal.  The  fact  is  that  this  synthesis  always  yields 
the  butane  with  boiling  point  +  i°.  This,  then,  is  normal  butane  and  the 
one  boiling  at  — 11.15"°  is  iso-butane.  The  synthesis  of  the  two  butanes 
from  the  two  propyl  iodides  may  now  be  used  to  prove  which  of  the  latter 
is  the  normal  and  which  the  iso  compound.  The  butane  which  we  have 
just  proven  to  be  normal  butane  and  which  boils  at  +  i°  is  always 
obtained  from  the  propyl  iodide  with  boiling  point  102.5°,  which  must 
therefore  be  normal  propyl  iodide.  Similarly  iso-butane  is  obtained 
from  the  propyl  iodide  boiling  at  89°,  and  this  must  be  iso-propyl 
iodide.  We  have,  then,  the  following  relationship  established  and  the 
compounds  with  the  definite  boiling  points  as  given  must  have  the 
constitution  assigned  to  them. 

CH3— CH2— CH2I-»CH3— CH2— CH2— CH8^- CH3CH2(I  +  2Na  +  I)CH2CH3 

Normal  propyl  iodide  Normal  butane  Ethyl  iodide 

B.  P.      102.5°  B.  P.      +  i° 

CH3— CH— CH3  -*    CH3— CH— CH3 
I  I 

I  CH3 

Iso-propyl  iodide  Iso-butane 

B.P.     89°  B.P.      -11.15° 

Analogous  to  the  synthesis  of  normal  butane  from  sodium  and  ethyl 
iodide  alone  is  the  fact  that  normal  propyl  iodide  alone  with  sodium 


HYDROCARBONS  OF  THE  METHANE  SERIES         2Q 

yields  a  hexane,  which  boils  at  69°  and  which  by  this  synthesis  must  be 
normal  hexane: 


CH3— CH2— CH2(I  +  2Na  +  I)CH2— CH2— CH3       — > 

Normal  propyl  iodide 

CH3— CH2— CH2— CH2— CH2— CH3  +  2NaI 

Normal  hexane,  B.P.  69° 

This  same  hexane  may  also  be  prepared  from  a  pentyl  iodide,  and  as 
the  hexane  has  the  normal  structure  the  pentyl  iodide  from  which  it  is 
made  must  similarly  be  normal  pentyl  iodide,  and  its  hydrocarbon  is 
normal  pentane.  By  a  series  of  such  reactions  the  exact  constitution 
of  each  butane,  pentane  and  hexane  and  their  iodides  has  been  established. 
It  has  been  found  that  in  each  group  of  isomeric  hydrocarbons  the 
normal  compound  is  the  one  having  the  highest  boiling  point.  The 
normal  hydrocarbons  themselves  form  a  gradually  ascending  series  as 
indicated  by  their  boiling  points,  while  each  group  of  isomeric  hydro- 
carbons forms  a  gradually  descending  series.  These  two  facts  of  an 
ascending  series  of  normal  compounds  and  a  descending  series  of  each 
group  of  isomeric  compounds  have  been  found  to  be  true,  not  only  for 
the  hydrocarbons,  but  for  each  series  of  substitution  products  of  these 
hydrocarbons.  This  emphasizes  in  a  striking  way  the  family  or  series 
relationship.  The  homologous  nature  of  each  such  series  of  organic 
compounds  is  thus  seen  to  be  something  fundamental  which  finds  its 
most  probable  explanation  in  our  conception  of  structure  or  constitution 
as  we  have  discussed  it. 

Names  of  Isomers. — As  we  have  just  stated,  the  names  of  the  two 
propyl  iodides  and  of  the  two  butanes  may  be  simply  normal  and  iso. 
In  each  group  of  isomers  where  only  two  are  possible  these  two  names 
are  sufficient  to  characterize  them  as  structurally  different  compounds, 
and  to  indicate  the  structure  of  each.  In  the  case  of  pentane,  however, 
three  isomers  are  known,  and  in  that  of  hexane  there  are  five.  In  all 
such  cases  where  there  are  more  than  two  isomers  we  must  devise  other 
names  and  these  names  should  be  such  as  to  fully  express  the  difference 
in  structure  between  the  isomeric  compounds. 

Systematic  Nomenclature. — That  compound  which  by  synthesis 
or  decomposition  is  shown  to  have  the  structure  represented  by  the 
straight  chain  formula  is  always  known  as  the  normal.  In  strictly 
systematic  nomenclature  this  name  is  often  omitted,  but  implied,  so 


30  ORGANIC  CHEMISTRY 

that  the  simple  unqualified  systematic  name  always  means  the  compound 
with  the  normal  constitution.  According  to  what  may  be  called  the  old 
system  of  nomenclature  the  other  isomeric  compounds  were  given 
names  which  indicate  the  radicals  linked  together  to  form  a  compound 
possessing  a  definite  constitution.  The  compounds  were  further  con- 
sidered as  derivatives  of  methane.  Let  us  take  two  of  the  five  isomeric 
hexanes  as  an  illustration.  Normal  hexane  or  simply  hexane  may  be 
prepared  by  the  action  of  sodium  upon  normal  propyl  iodide  (p.  29) 
which  proves  its  constitution  to  be  that  of  di-propyl  or  propyl  propane, 
viz.,  < 

CH3—  CH2—  CH2(I  +  2Na  +  I)CH2—  CH2—  CH3       —  > 

Propyl  iodide 

(CH3—  CH2—  CH2)—  (CH2—  CH2—  CH3) 

Normal  hexane 
Propyl  propane 

The  same  hexane,  however,  may  also  be  prepared  from  pentyl  iodide 
and  methyl  iodide  with  sodium  so  that  it  may  be  represented  as  con- 
taining the  two  radicals  normal  pentyl  and  methyl,  and  could  be  called 
pentyl  methane, 


CH3—  CH2—  CH2—  CH2—  CH2—  (I  +  2Na    +    I)—  CH3    -  > 

Pentyl  iodide  Methyl  iodide 

(CH3—  CH2—  CH2—  CH2—  CH2)—  CH3 

Normal  hexane 
Pentyl  methane 

Still  another  synthesis  yields  the  same  hexane  by  which  it  may  be 
shown  to  be  represented  by  the  two  radicals  ethyl  and  normal  propyl, 
both  substituted  in  methane  as  follows: 

(CH3—  CH2)—  CH2—  (CH2—  CH2—  CH3) 

Normal  hexane 
Ethyl  propyl  methane 

Now  each  of  these  groupings  of  the  radicals  is  based  upon  definite 
reactions  of  synthesis  so  that  they  are  all  correct.  Also  they  all  indi- 
cate clearly  the  exact  constitution  of  the  compound  as  only  a  normal 
structure  can  result  from  the  union  of  either  of  these  sets  of  radicals. 
In  the  case  of  this  hexane  of  course  we  need  no  other  name  than  normal, 
and  the  others  are,  therefore,  discarded.  For  the  isomeric  hexanes, 
however,  we  do  need  other  names,  but  we  shall  see  that  in  each  case 
there  are  several  names  that  may  be  used. 


HYDROCARBONS    OF    THE    METHANE    SERIES  31 

Just  as  we  have  shown  what  names  may  be  applied  to  normal 
hexane  it  may  also  be  shown  that  the  hexane  with  boiling  point  of  62° 
may  be  synthesized  by  three  sets  of  reactions  which  prove  that  it 
has  the  structure  represented  by  the  following  formula  which  is  identi- 
cal in  the  three  cases.  The  names  assigned  indicate  the  grouping  of 
the  radicals  as  effected  by  the  different  alkyl  radicals  used  in  each 
synthesis.  In  the  formula  these  radicals  are  enclosed  in  parentheses. 

(i)  Di-methyl  normal  propyl  methane, 

(CH3)—  CH—  (CH2—  CH2—  CH3) 


(2)  Ethyl  iso-propyl  methane,  (CH3—  CH)—  CH2—  (CH2—  CH3) 

I 
(CH3) 

(3)  Methyl  iso-butyl  methane,  (CH3—  CH—  CH2)—  CH2—  (CH3) 

I 
(CH,) 

In  the  same  way  it  may  be  shown  that  the  other  three  hexanes  may 
each  be  given  several  different  names.  It  must  be  emphasized  that 
all  of  these  names  for  any  one  compound  indicate  the  same  structure. 
The  difference  in  the  names  depends  simply  upon  the  way  in  which  we 
divide  the  group  of  carbons  into  smaller  groups  or  radicals,  and  this 
depends  on  definite  reactions,  each  one  of  which  is  correct,  and  each 
indicates  the  same  structure  through  a  different  but  correct  grouping. 
We  see,  therefore,  right  at  the  beginning  of  our  study  the  confusion 
which  may  arise  by  the  use  of  different  names  for  the  same  compound, 
and  the  difficulty  of  selecting  one  name  as  more  desirable  than  the 
others. 

Official  Nomenclature.  —  In  order  to  avoid  this  confusion  a  congress 
of  chemists  which  met  in  Geneva  in  1892  adopted  an  Official  System  of 
Nomenclature.  The  names  according  to  this  system  and  known  as  the 
Official  Names  (abbreviated  O.  N.)  are  now  used  in  all  reference  books 
and  dictionaries,  such  as  Beilstein,  "Handbuch  der  Organischen 
Chemie"  and  Richter,  "Lexikon  der  Kohlenstoff-Verbindungen."  It 


32  ORGANIC  CHEMISTRY 

would  be  out  of  place  in  a  book  such  as  this  to  explain  the  entire  system 
or  to  adopt  it  absolutely,  but  enough  can  be  given  at  this  point  in  con- 
nection with  the  isomeric  hydrocarbons  to  enable  the  student  to  grasp 
some  of  the  fundamental  ideas  and  to-  understand  the  official  names  as 
they  may  be  given.  For  many  of  the  simpler  compounds  considered 
in  this  book  both  the  official  name  and  the  commonly  accepted  name 
will  be  given,  the  latter  being  usually  given  first.  It  should  be  said 
that  in  neither  of  the  reference  books  mentioned  nor  in  any  other  book, 
so  far  as  the  author  knows,  is  the  official  system  used  exclusively  or 
without  more  or  less  independent  choice.  Old  and  commonly  used 
names  are  difficult  to  replace  and  they  will  probably  always  be  used. 
In  the  case  of  new  compounds,  however,  the  official  system  is  universally 
adopted. 

In  the  official  nomenclature,  instead  of  referring  compounds  to  meth- 
ane as  derivatives  of  it,  they  are  considered  as  derivatives  of  that 
hydrocarbon  corresponding  to  the  longest  straight  carbon  chain  which  is 
present  in  the  compound  as  represented  by  the  established  structural 
formula.  The  position  of  the  substituting  elements  or  radicals  is 
indicated  by  numbers  or  by  Greek  letters  applied  to  the  carbons  of  the 
straight  chain,  i.e.,  the  carbons  of  the  root  hydrocarbon,  beginning 
with  the  end  carbon  nearest  to  the  substituting  radical  or  element.  The 
normal  compounds  simply  retain  the  hydrocarbon  name  so  that  the 
simple  names  pentane,  hexane,  heptane,  mean  in  every  case  the  nor- 
mal hydrocarbon.  The  branched  chain  or  isomeric  compounds  are, 
therefore,  the  only  ones  which  we  need  to  consider  now. 

Iso-butane  has  the  structure 


i          2         3 
CH3— CH— CH3 

2 -Methyl  propane 
CH3 

Instead  of  considering  it  as  a  derivative  of  methane  it  is  considered  as 
a  derivative  of  propane  because  three  carbons  is  the  longest  straight 
chain  of  carbon  atoms  present,  and  the  three  carbon  hydrocarbon  is 
propane.  It  is  then  methyl  propane  in  which  the  methyl  is  linked  to 
carbon  atom  number  two.  Its  name  is  written  as  follows:  2-methyl 
propane. 


HYDROCARBONS    OF    THE   METHANE    SERIES  33 

The  pentane  which  boils  at  30°  was  formerly  called  di-methyl  ethyl 
methane  or  simply  iso-pentane,  its  structure  being: 

i  23  4 

(CH3)— CH— (CH2— CH3) 

2 -Methyl  butane 

(CH3) 

In  this  formula  four  carbons  is  the  longest  straight  chain,  and  it  is, 
therefore,  a  butane  derivative  with  methyl  linked  to  carbon  2.  Its 
official  name  is  2-methyl  butane.  The  pentane  boiling  at  9°  is  by  the 
old  system  tetra-methyl  methane. 

CH3 

CH3— C— CH3    2  -2  -Di-methyl  propane 
CH3 

In  this  compound  three  carbons  constitute  the  longest  unbranched 
chain  and  in  this  two  methyl  groups  are  linked  to  carbon  atom  2.  We 
write  this  name  2 -2 -di-methyl  propane. 

The  hexane  boiling  at  64°  was  called  methyl  di-ethyl  methane,  as 
shown  in  the  first  formula.  If,  however,  we  write  this  structural 
formula  differently,  but  representing  the  same  structure,  we  see  that  the 
longest  unbranched  chain  consists  of  five  carbons. 

345  12345 

(CH3)— CH— (CH2— CH3)  CH3— CH2— CH— CH2— CH3 

1  or  I 
(CH2— CH3)                                                     CH3 

2  I 

3-Methyl  pentane 

It  is  then  a  pentane  derivative  (i.e.)  3 -methyl  pentane.  The  hexane 
boiling  at  62°,  viz.,  di-methyl  propyl  methane  is  2-methyl  pentane: 

(CH3)— CH— (CH2— CH2— CH3) 

2 -Methyl  pentane 
(CH,) 


34 


ORGANIC  CHEMISTRY 


The  hexane  boiling  at  58°  was  di-methyl  iso-propyl  methane.    Its 
official  name  is  2 -3 -di-methyl  butane : 

(CH3)— CH— (CH3)  CH3— CH— CH— CH3 

or 
(CH3  — CH— CH3)  H3C       CH3 

2-3-Di-methyl  butane 

The  hexane  boiling  at  48°  was  tri-methyl  ethyl  methane.  It  is  2-2- 
di-methyl  butane : 

(CH3) 

I 
(CH3)— C— (CH2— CH3)  2-2-Di-methyl  butane. 

I 
(CH3) 

This  may  at  first  seem  very  confusing,  but  it  will  be  well,  if  at  the  be- 
ginning the  fundamentals  of  this  official  nomenclature  are  mastered. 
The  whole  system  will  then  become  clearer  as  we  proceed,  and  the  names 
will  become  more  familiar.  It  may  seem  hardly  necessary  with  the 
relatively  small  number  of  compounds  which  we  shall  study  to  use  the 
official  names.  We  must  realize,  however,  that  these  few  compounds 
constitute  only  an  exceedingly  small  part  of  the  more  than  200,000 
known  compounds  made  up,  for  the  most  part,  of  the  same  four  or 
five  elements.  An  understanding,  or  more  particularly  a  working 
knowledge,  of  books  of  reference  and  original  literature  concerning  these 
compounds  can  only  be  gained  through  familiarity  with  this  system 
of  official  nomenclature. 

In  order  to  help  fix  the  matter  in  our  mind,  and  to  bring  the 
facts  we  have  been  discussing  together,  the  following  comparative  table 
may  be  of  value. 


HYDROCARBONS    OF   THE   METHANE   SERIES 


35 


•0 

d 

i 

S 

i 

if 

j 

iso-propyl 

i 

"3 

^        ^ 

JK  ^  5 

H 

a  ** 

p, 

Names  by  < 

JH 

«   S   ?   o 

1^S 

S-2.  * 

nl! 

||5S 

4) 

S 

i 
I 

Hezanes 
Normal  hea 
Methyl  di-c 

f 

S 

*£>    4> 

.     1| 

s   £! 

Tri-methyl 
ane 

a 

o  ^ 

Q 

*O 

„ 

La 

a 

11 

O  ^ 

,°L 

r3     §* 

CO 

La 

L  a 

a 

W« 

'w 

g  60 

g 

8? 

g- 

O 

a 
o 

-2  a 

L 

La1 

^ 

u 

a  a 

a    S 

L 

Structural 
old  syst( 

tf  . 

aa    a 

tr° 

a  a 
o  o 

(£HO) 

1 

0)—  HO—  (£HO) 
HO—  'HO—  8HO 

a 
a    T    a 

0  —  0  —  0 

a 

0 

CHa—  CH«—  CH 
(CHa—  CH2)—  C 
1 

B^ 
o- 

i 

a 

0 

9.—^ 
i 

a  a    A 

-^9—^ 
i    a 
a 

0 

a 
o 

a    T    a 

0  —  0  —  0 

i 

0 

O    tf) 

o  o 

°0 

°o  *b 

°o 

°0 

°o 

S 

+  T 

t-    O 

a 

o  4 

5 

oo 

V) 

CO 

a 

a 

«a 

CO 

a 

"3 
^ 

"o 

*• 

w 

a 

o 

W  . 

aa    a 

tro 

a—  CHa—  CHa—  CHa—  C 
3—  CH—  CH2—  CHa 
1 
CHa 

s  ?  * 

O  —  O  —  O 

1 

o  o  — 

LL 

a  a 
o  o 

LL 

o 
o 

o- 

L 

a 
o 

1 
a    a 

0-0 

wa 

jn 

n 

a 
o 

d  ?  a 

o  —  o  —  o 

a  a 

a  a 

a 

a  a 

a 

a 

a 

o  o 

o  o 

o 

o  o 

o 

0 

o 

i 

1 

1 

V 

S 

oi 

:  * 

8 

i 

1 

1 

| 

C 

j 

1 

1 

O 

1 

1 

'o 
O 

w    fl  tJ 

s|| 

1 

nil 

1 

Q 

S 

a  -2  S 

§    H  JS 

,!, 

g  SS 

S 

"5   «     «H 

0    04     A 

^ 

gw  i, 

N 

N 

CQ 

£ 

a 

36  ORGANIC  CHEMISTRY 

Higher  Hydrocarbons. — It  will  not  be  necessary  to  dwell  at  any 
length  upon  the  higher  members  of  the  series.  The  names,  formulas, 
physical  constants  and  the  number  of  isomers  known  or  isolated  are 
given  in  the  table  (p.  19).  Further  facts  in  regard  to  any  known  indi- 
vidual may  be  obtained  by  referring  to  such  books  as  Beilstein  and 
Richter. 

As  the  number  of  carbon  atoms  increases  the  possibilities  of  iso- 
merism  increase  likewise,  and  very  rapidly  as  shown  by  the  following 
table: 


TABLE  III— ISOMERIC  HYDROCARBONS 


Hydrocarbon 

Number  of  isomers 
theoretically 
possible 

Number  of 
known  com- 
pounds 

Butanes  C4Hio               

2 

2 

Pentanes   CsHi2 

3 

3 

Hexanes   CeHi4 

c 

5 

Heptanes   CyHie              

9 

5 

Octanes   CsHig                              

18 

2 

Nonanes   CgH2o 

•2C 

3 

Decanes   CioH22 

7C 

6 

Undecanes   CnH24                  

159 

i 

Dodecanes   Ci2H26 

•zee 

i 

Tridecanes,  CiaH28  

802 

i 

The  higher  members  above  heptadecane  are  wax-like  solids  at 
ordinary  temperatures.  They  occur  naturally  in  petroleum  and  ozo- 
kerite, and  are  obtained  as  mixtures  in  the  higher  distillation  products 
of  petroleum,  viz.,  in  paraffin  oil,  paraffin  and  vaseline.  They  are 
also  obtained  as  distillation  products  from  coal,  wood  and  fish  oil. 
The  separation  of  individual  hydrocarbons  by  the  fractional  distilla- 
tion of  these  mixtures  is  a  very  difficult  operation,  so  that  the  prepara- 
tion of  the  pure  hydrocarbons  is  always  accomplished  by  means  of 
one  of  the  general  methods  of  synthesis  from  related  compounds. 
These  methods  are  those  for  preparing  the  hydrocarbons  from  the 
next  lower  hydrocarbon,  discussed  on  pages  16-29,  and  those  for  pre- 
paring hydrocarbons  from  alcohols  and  unsaturated  hydrocarbons 
which  will  be  discussed  when  these  compounds  are  considered. 


PETROLEUM  37 

Petroleum 

The  consideration  of  petroleum  belongs  with  our  study  of  the  hy- 
drocarbons for,  though  other  compounds  are  present,  the  greater  part 
are  hydrocarbons.  The  hydrocarbons  found  in  petroleum  are  not,  how- 
ever, all  members  of  the  methane  or  saturated  series  which  we  have 
been  discussing  but  represent  practically  every  group  or  series  of  hydro- 
carbons some  of  which  we  shall  study  later.  Nevertheless  it  seems 
better  to  present  the  subject  at  this  time  in  connection  with  the  first 
series  of  hydrocarbons  inasmuch  as  the  most  important  facts  and 
problems  in  connection  with  petroleum  are  not  those  of  constitution 
or  of  the  systematic  relationship  of  the  constituents  to  other  organic 
compounds,  but  are  those  of  an  industrial  nature  involving  largely 
physical  factors. 

Occurrence. — The  geographical  distribution  of  petroleum  in  the 
earth  is  very  wide  and  only  a  few  large  land  areas  are  found  to  be 
without  it.  Africa,  the  very  northern  part  of  North  America  and  the 
northern  part  of  Siberia  are  practically  without  any  known  'deposits. 
The  most  abundant  fields  at  present  are  (i)  The  United  States;  Penn- 
sylvania, Ohio,  Indiana,  Texas  and  California;  (2)  Russia;  especially 
in  the  region  of  the  Caspian  Sea,  the  Baku  peninsula;  (3)  Austria; 
Galicia;  (4)  Mexico;  (5)  Italy,  Roumania,  Alsace,  Burma,  Java  and 
Japan.  Of  these  various  regions  the  two  largest,  viz.,  the  United 
States  and  Russia,  furnish  at  present  over  90  per  cent  of  the  world's 
supply. 

Physical  Properties. — Crude  petroleum  is  a  more  or  less  dark 
colored  fluorescent  liquid  with  a  characteristic  odor.  The  specific 
gravity  usually  lies  between  0.74  and  0.97  but  in  a  few  cases  is  as 
high  as  1.3. 

Chemical  Character. — In  its  chemical  character  petroleum  is  not 
a  single  compound  but  is  a  very  complex  mixture  of  a  large  number  of 
compounds.  Its  approximate  percentage  composition  is,  carbon  87.0 
per  cent,  hydrogen  13.0  per  cent,  with  small  and  varying  amounts  of 
oxygen,  sulphur  and  nitrogen.  A  more  detailed  statement  of  its  com- 
position may  be  given  as  follows:  Carbon,  79.5-88.7  per  cent,  hydro- 
gen 9.6-14.8  per  cent,  nitrogen  0.15-1.1  per  cent,  sulphur  0.06-3.0 
per  cent  and  oxygen  in  traces.  There  is  also  a  slight  ash  amounting 
to  about  o.io  per  cent  which  may  contain  traces  of  calcium,  iron, 
aluminium,  copper,  silver,  arsenic  and  phosphorus.  The  oxygen  com- 


3 8  ORGANIC  CHEMISTRY 

pounds  present  are  phenols  and  organic  acids  usually  amounting  to  less 
than  i.o  per  cent.  Nitrogen  which  is  found  in  Texas  petroleum  to 
the  amount  of  i  .o  per  cent  is  usually  much  less  than  this  and  is  present 
as  organic  bases  and  ammonia.  Sulphur  which  is  usually  present  in 
small  amounts,  0.1-0.15  per  cent  is  found  in  the  petroleums  of  Ohio, 
Indiana,  Texas  and  Virginia  in  amounts  as  high  as  i  .3  per  cent  and  even 
3.0  per  cent.  It  is  present  as  mercaptans,  thiophene  and  some  other 
compounds.  As  the  presence  of  sulphur  compounds  is  very  objection- 
able on  account  of  their  odor,  and  on  account  of  the  products  of 
volatilization  and  combustion,  their  removal  is  necessary.  This 
caused  much  trouble  originally  in  the  refining  of  the  oils  from  these 
districts. 

While  all  of  these  various  compounds  have  been  found  to  be  present, 
the  predominating  constituents  are  hydrocarbons.  The  individual  hy- 
drocarbons that  have  been  found  are  very  many,  probably  over  one 
hundred,  but  they  are  practically  all  representatives  of  three  main  series 
and  petroleums  from  different  regions  are  characterized  by  a  predomi- 
nence  of  one  series  over  the  others.  The  principal  series  found  are 
(i)  Hydrocarbons  of  the  Methane  or  Saturated  Series.  The  petroleums 
characterized  by  these  hydrocarbons  are  those  of  Pennsylvania,  Ohio, 
Indiana  and  Galicia.  (2)  Hydrocarbons  of  the  Ethylene  U maturated 
Series.  These  are  characteristic  of  the  petroleums  of  California  and 
Burma.  (3)  Hydrocarbons  of  the  Cyclic  Series.  The  saturated  cyclic 
hydrocarbons  known  as  naphthenes  are  characteristic  of  Russian 
(Baku)  petroleum  and  are  also  found  in  that  from  Galicia.  In  some 
cases  also  these  petroleums  contain  as  much  as  10  per  cent  of  unsatu- 
rated  cyclic  hydrocarbons  of  the  benzene  series.  The  higher  members 
of  the  methane  series  of  hydrocarbons,  which  are  present  especially 
in  the  product  known  as  paraffin,  are  found  in  very  different  amounts. 
American  petroleum  contains  usually  about  2.5-3.0  per  cent,  while  the 
Russian  oil  contains  only  about  0.25  per  cent.  On  the  other  hand,  the 
petroleums  of  Java,  India  and  some  from  Roumania  contain  an  excep- 
tionally large  amount  of  these  solid  hydrocarbons,  even  as  much  as  40 
per  cent,  which  gives  these  oils  a  very  high  specific  gravity. 

Distillation  Products. — The  importance  of  petroleum  as  a  commer- 
cial substance  lies  in  the  wide  industrial  use  of  the  various  products 
obtained  from  it  by  distillation.  As  petroleum  is  a  mixture  of  gaseous 
liquid  and  solid  hydrocarbons  both  it  and  its  distillation  products  are 


PETROLEUM 


39 


combustible  substances.     The  most  important  usee  of  the  products  are 
therefore  as  sources  of  heat  and  light. 

Heat  of  Combustion. — In  Table  IV  there  is  given  in  Calories 
(large)  per  gram  the  heat  of  combustion  of  petroleum  from  different 
regions  compared  with  two  of  the  hydrocarbons  and  with  some  other 
substances.1 


TABLE  IV. — HEAT  OF  COMBUSTION  OF  PETROLEUM,  ETC. 


Substance 


Calories  (large) 
per  gram 


Methane 

Ethylene 

Petroleum,  Russian  (Balakhany) 

Petroleum,  light,  Russian  (Baku) 

Petroleum,  heavy,  Russian  (Baku) 

Petroleum,  heavy,  Pennsylvania 

Petroleum,  light,  West  Virginia 

Petroleum,  heavy,  West  Virginia 

Petroleum,  light,  Pennsylvania 

Petroleum,  American  (average) 

Petroleum,  Alsace 

Coal 

Coke 

Peat '. 

Wood. . 


13-065 
11.805 
11.700 
11.460 
10.800 
10.672 
10.223 
10. 180 

9-963 
9.771 
9.708 

7.500 
6.500 
4-Soo 
2.800 


In  the  process  of  distillation  the  petroleum  is  subjected  to  fraction- 
ation.  The  fractions  like  petroleum  itself,  are  not  single  compounds 
but  are  mixtures  of  hydrocarbons  mainly.  The  fractions  obtained  are 
controlled  more  or  less  by  the  demands  of  the  trade  and  may  thus 
vary  within  moderate  limits.  The  fractions  are  also  dependent  upon 
the  crude  material,  i.e.,  the  region  from  which  the  petroleum  came  and 
also  somewhat  upon  the  refinery  where  the  distillation  is  carried  out. 
Any  data  that  may  be  given,  therefore,  in  the  following  tables  must  be 
considered  in  this  light  and  as  indicating  general  facts,  approximate 
limits  of  boiling  point,  specific  gravity,  etc. 

:The  data  in  Tables  IV,  V,  VI  are  taken  from  "Petroleum  and  Its  Products," 
Boverton  Redwood,  London,  1896,  pp.  190,  191,  194,  203. 


40  ORGANIC  CHEMISTRY 

Light  Oils. — The  boiling  point  of  petroleum  from  different  regions 
covers  quite  a  temperature  range,  viz.,  from  74°  to  135°.  When  dis- 
tilled the  first  large  fraction,  passing  over  below  130°  or  150°  yields 
products  known  as  light  oils.  The  fraction  is  again  distilled  and  yields 
the  following  oils: 

B.P. 

Petroleum  ether  and  rhigoline 40°-  7°° 

Gasoline 7°°-  80° 

Benzine 8o°-ioo° 

Ligroine ioo°-i 20° 

Cleaning  oil. i2O°-i5o° 

Illuminating  or  Burning  Oils. — The  second  large  fraction  with  a 
range  of  boiling  point  between  150°  and  300°  yields  burning  oils,  the 
different  sub-fractions  being  used  in  lamps  for  illumination.  This 
distillate  by  further  fractionation  yields  the  following  products  which 
are  differentiated  by  specific  gravity  rather  than  boiling  point. 


Sp.  Gr. 

Kaiser  oil 780- .  800 

Kerosene  (American) 800- .  810 

Kerosene  (Russian) 820-. 825 

Prime  white  oil 800- .  806 

Standard  white  oil. 808-. 812 

Astraline 850-.  860 


Lubricating  or  Heavy  Oils. — Oils  which  distil  above  300°  are  used 
for  lubricating  purposes  and  the  different  smaller  fractions  into  which 
this  portion  of  the  distillate  is  divided  are  used  as  different  grades  of 
lubricating  oils. 

The  following  table  gives  the  various  smaller  fractions  usually 
obtained  with  the  boiling  points  and  specific  gravities. 


PETROLEUM 


TABLE  V. — COMMERCIAL  DISTILLATION  PRODUCTS  OF  PETROLEUM 
Light  Oils,  B.P.  40°- 1 50° 


B.P. 


Sp.  Gr. 


Petroleum  ether  (Rhigoline) 40°-  70°  o .  650-0 . 660 

Benzine  (U.  S.) 50°-  60°  0.670-0.675 

Gasoline 70°-  80°  0.640-0.667 

Benzine  (English) 8o°-ioo°  o. 667-0. 707 

Ligroine ioo°-i2o°  o.  707-0. 722 

Cleaning  oil i2O°-i5o°  o.  722-0. 737 

Illuminating  Oils,  B.P.  i5o°-3oo° 

Kaiser  oil o.  780-0.800 

Kerosene  (American) 0.800-0.810 

Kerosene  (Russian) 0.820-0.825 

Prime  white  oil t.  .  o .  800-0 . 806 

Standard  white  oil 0.808-0.812 

Astraline o .  850-0 . 860 

Lubricating  Oils,  B.P.  300°- 

Solar  oil 0.860-0.880 

Mixing  oil 0.880-0.890 

Spindle  oil  1. 0.895-0.900 

Spindle  oil  II o .  900-0 . 906 

Machine  oil  I o .  906-0 . 910 

Machine  oil  II 0.910-0.915 

Cylinder  oil  (bright) ." 0.915-0.920 

Cylinder  oil  (dark) o .  920-0 . 950 

Vulcan  oil , 0.910-0.960 


The  following  table  gives  the  percentage  yield  as  'obtained  from 
different  petroleums  of  (a)  light  oils,  benzine  and  gasoline;  (b)  illumi- 
nating oils,  kerosene;  (c)  lubricating  oils,  including  solid  products  and 
(d)  residue,  coke. 


42  ORGANIC  CHEMISTRY 

TABLE  VI.— PERCENTAGE  YIELD  OF   COMMERCIAL  PRODUCTS  FROM  DIFFERENT 

PETROLEUMS 


Source  of  petroleum 

Sp.  Gr. 

Light  oils; 
benzine, 
gasoline, 
per  cent 

Illuminating 
oils; 
kerosene, 
per  cent 

Lubricating 
oils  and 
solid  prod- 
ucts, per  cent 

Coke, 
per  cent 

Pennsylvania  

O.SlO 

20.0 

50,0 

25-3 

1  .  12 

Pennsylvania  

o.  797 

21  .O 

74.1 

1.36 

Pennsylvania. 

0.787 

32.0 

64.4 

Pennsylvania  
Pennsylvania  

0.802 
0.788 

21.0 

18.1 

74-3 
71.  i 

0.8 

14 
O.  I 

Ohio  (Macksburg)...  . 
Ohio  (Lima)      

0.829 
0.839 

II  .0 

83 

49.0 
o 

35-7 
6.9 

1.8 

4-  ! 

Wyoming  
California  
Mexico  
Russia  
Russia      

0.911 

0.844 
0.874 
0.873 
0.780 

2.5 

12.5 

6.3 

48.9 

27-5 

22.0 

37-o 

32.5 

43.9 

S3-o 
42.6 

62.  2 

57-i 

II  .0 

10.2 

o-5 
3-P 

Russia  
Russia  

0.853 
0.884 

20.  o 
20.  o 

40.0 
20.  o 

3S-o 
50.0 

5-9 

Galicia 

o  .  84  <? 

12  .  5 

37-S 

40.  7 

8.3 

Alsace  
Zante    .  .           

0.886 
i  .02 

4.0 

3i-4 

52-7 
76.2 

7-9 

18.4 

Benzene,  Gasoline. — Two  products  obtained  from  petroleum  are 
of  especial  interest  and  importance.  One  of  these  is  the  individual 
hydrocarbon  benzene,  which  is  obtained  in  much  larger  yields  from  coal 
tar  and  is  of  importance  in  connection  with  the  manufacture  of  dyes  and 
explosives.  The  other  is  the  commercial  product  known  as  gasoline, 
which  is  a  mixture  of  hydrocarbons  and  is  used  largely  as  motive  power 
in  gasoline  engines  for  automobiles  and  air  planes.  Distinction  should 
be  made  between  benzene,  which  is  a  single  compound  and  benzine, 
which  is  a  mixed  commercial  product  containing  numerous  hydrocar- 
bons and  which  is  similar  to  gasoline  and  kerosene.  (See  Part  II.) 
Almost  all  crude  petroleums  yield  some  benzene  but  in  no  large 
amount,  while  gasoline  is  one  of  the  light  oil  fractions  always  obtained. 
Because  of  the  value  of  these  two  products  much  attention  has  been 
given  during  recent  years  to  increasing  the  yield.  The  study  of  the 
temperature  and  pressure  conditions  affecting  the  production  of  ben- 
zene and  gasoline  has  been  thoroughly  gone  into  with  the  result  that 
several  processes  have  been  patented.  The  most  important  ones  are 


PETROLEUM  4  ^ 

those  of  the  Standard  Oil  Co.,  Hall  of  England  and  Rittman  of  the  U.  S. 
Bureau  of  Mines.  The  principle  involved  in  all  of  these  is  known  as 
cracking.  The  petroleum  either  in  the  liquid  phase  or  gaseous  phase  is 
super-heated  under  pressure  and  then  allowed  to  expand  and  distil. 
By  these  processes  the  yield  of  both  benzene  and  gasoline  has  been 
materially  increased  so  that  a  larger  per  cent  of  these  products  is  ob- 
tained at  the  expense  of  either  other  light  oil  constituents  or  at  the 
expense  of  the  illuminating  oil  fraction. 

Vaseline  and  Paraffin. — Two  solid  products  obtained  from  petro- 
leum are  the  common  pharmaceutical  substance  vaseline,  a  hydro- 
carbon mixture  melting  at  about  35°  and  the  white  solid  known  as 
paraffin,  also  a  hydrocarbon  mixture  melting  at  about  4O°-6o°.  The 
properties  and  uses  of  these  two  substances  are  too  common  to  require 
any  further  description. 

Tar  and  Coke. — The  tar  residue  obtained  from  petroleum  is  used 
for  various  purposes  such  as  water-proofing,  wood-preserving,  road- 
making,  etc.,  in  a  similar  way  to  the  tar  obtained  from  coal  distilla- 
tion. The  coke  obtained  as  the  final  solid  residue  is  used  as  fuel. 

Origin  of  Petroleum. — The  theories  as  to  the  origin  of  petroleum 
are  of  three  kinds,  (a)  animal  origin,  (b)  vegetable  origin,  (c)  inorganic 
origin,  (a)  The  first  theory  that  petroleum  is  of  animal  origin  assumes 
that  it  originated  from  the  geologic  decomposition  of  sea  animals.  In 
such  a  decomposition  most  of  the  nitrogen  of  the  animal  protein  would 
be  lost  but  there  would  naturally  be  some  left  in  the  petroleum.  That 
most  petroleums  contain  only  traces  of  nitrogen  has  been  considered  as 
an  objection  to  the  theory  of  animal  origin  but  the  finding  of  Texas 
petroleum  with  as  much  as  i.o  per  cent  of  nitrogen  gives  support  to 
the  theory.  The  theory  has  been  advocated  especially  by  Engler 
and  Holde.  The  former,  by  the  distillation  of  fish  oil  under  pressure, 
showed  that  animal  fats  may  be  converted  into  hydrocarbons  with 
the  formation  of  products  analogous  to  crude  petroleum,  (b)  The 
theory  of  vegetable  origin  is  supported  by  the  similarity  of  the  com- 
pounds found  in  petroleum  with  the  products  obtained  by  the  distil- 
lation of  such  vegetable  substances  as  wood,  peat  or  coal.  It  is  opposed, 
however,  by  the  fact  that  petroleum  deposits  are  not  found  in  the  strata 
of  the  earth  which  contain  plant  remains,  (c)  The  theory  of  the  in- 
organic origin  of  petroleum  has  been  held  by  such  men  as  von  Hum- 
boldt,  Mendelejeff,  and  more  recently  by  Moissan.  The  latter  has 


44  ORGANIC  CHEMISTRY 

shown  that  numerous  metallic  compounds  of  carbon  known  as  carbides 
may  be  prepared  by  means  of  the  electric  furnace  and  that  these  car- 
bides, by  the  action  of  water,  decompose  yielding  various  hydrocar- 
bons both  saturated  and  unsaturated.  The  latter  by  the  action  of 
hydrogen  in  the  presence  of  a  catalyser  yield  saturated  compounds. 


AlfC8    +    i2H2O        —  *        3CH4    +    4A1(OH)3 

Aluminium  Methane 

carbide 

CaC2    +      2H2O  -*         C2H2    +    Ca(OH)2 

Calcium  Acetylene 

carbide 

Further  details  in  connection  with  the  geologic  origin  and  occur- 
rence of  petroleum  may  be  obtained  from  special  books  on  the  subject. 


II.     MONO-SUBSTITUTION  PRODUCTS  OF  SATURATED 
HYDROCARBONS 

(A)  MONO -HALOGEN  SUBSTITUTION  PRODUCTS 
ALKYL  HALDIES     R— X     HALOGEN  ALKANES 

The  alkyl  halides,  as  has  been  previously  stated,  are  compounds 
containing  an  alkyl  radical  joined  to  a  halogen  element;  i.e.,  iodine, 
bromine,  chlorine  or  fluorine.  They  are  mono-halogen  substitution 
products  of  the  paraffin  hydrocarbons.  The  general  facts  in  regard  to 
them  have  been  so  fully  discussed,  in  connection  with  their  relation  to 
the  ideas  of  substitution  and  isomerism  and  to  the  synthetic  building 
up  of  the  hydrocarbons,  that  there  is  little  to  add  except  to  mention  the 
more  important  individual  compounds,  and  to  give  their  occurrence 
and  uses.  The  following  table  gives  the  chlorides,  bromides  and  io- 
dides of  the  first  four  hydrocarbons  with  their  boiling  points  and 
specific  gravities. 

The  homologous  character  of  this  series  may  be  seen  by  examina- 
tion of  the  table.  The  boiling  points  rise  as  we  go  up  the  series  just 
as  they  did  in  the  case  of  the  hydrocarbons.  The  lowest  is  methyl 
chloride  with  boilingpoint  —23.7°,  the  highest,  butyl  iodide,  b.  p.  130°. 
Also  the  boiling  points  of  the  members  of  each  isomeric  group  decreases, 
e.g.,  primary  normal  butyl  iodide  is  130°  and  tertiary  butyl  iodide  is 
1 00°.  It  will  be  seen  also  that  there  is  a  similar  rise  in  the  boiling 
points  from  the  chlorides  to  the  bromides  and  then  to  the  iodides  giving 
us  a  double  homologous  relationship.  The  specific  gravities  become 
lower  as  we  go  up  the  series  which  is  the  reverse  of  the  same  property 
in  the  homologous  series  of  hydrocarbons.  This  lowering  becomes 
more  rapid  within  the  isomeric  groups.  As  we  go  from  the  chlorides 
to  the  bromides  and  iodides,  however,  we  find  that  the  specific  gravity 
increases. 

Isomerism  of  Alkyl  Halides. — In  discussing  the  question  of  iso- 
merism  in   connection   with   the  butanes  and  pentanes  (pp.  21-29). 
we  found  that,  while  the  two  isomeric  butanes  really  yield  four  methyl 
substitution  products,  i.e.,  pentanes,  two  of  them  possess  the  same 

45 


46 


ORGANIC  CHEMISTRY 


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;     ';       jg^|g-x 

la         ^ 

«  o           :  tJ         g 

i  U  t!gLl!gl 

go  —  o|  gx_ci-o 

li!|sii|gLj|g   ! 

11       55      ^L 

SwS             (QfiM        COis                  ^5 

H                                 HA 

ALKYL   HALIDES  47 

structure  so  that  only  three  are  possible  which  agrees  with  the  facts, 
as  three  and  only  three  are  known.  When,  however,  we  substitute 
iodine  in  the  two  isomeric  butanes  we  find  that  four  butyl  iodides  are 
possible,  all  of  which  are  different  and  all  of  which  are  known.  This 
will  be  seen  from  the  following  scheme  of  relationships. 


CHr-CH2—  (CHa—  I) 

Primary  (normal)  butyl  iodide 
z  —  lodo  butane  B.P.  130° 

CH3—  CH2—  CHr-CHs 

Normal  butane  M.P.  i° 

CH3  —  CH^v 


CH/ 

Secondary  (normal)  butyl  iodide 
2  —  lodo  butane  B.P.  119° 

CH3—  CH—  (CH2—  I) 
CH3 

(Primary)  Iso-butyl  iodide 

i  —  lodo  2  —  methyl  propane 

B.P.  119° 

CH3—  CH—  CH3 

I 
CH3 

Iso-butane  M.P.  -11.5° 


CH3 

Tertiary  (Iso)  -butyl  iodide 

2  —  lodo  2  —  methyl  propane 

B.  P.  100° 

Primary,  Secondary  and  Tertiary  Compounds.  —  The  naming  of 
these  four  isomeric  butyl  iodides  brings  us  to  the  consideration  of  a 
new  point  in  the  nomenclature  of  organic  compounds.  In  the  first 
compound,  which  has  the  straight  chain  structure,  i.e.,  a  normal  com- 
pound, the  carbon  atom  in  the  group  containing  the  halogen,  viz., 
(CH2I)  is  linked  to  one  other  carbon  atom.  The  same  condition  is  found 
in  the  third  compound  where  the  structure  is  that  of  an  iso  or  branched 
chain.  In  the  second  compound,  however,  which  is  also  normal,  the 


48  ORGANIC  CHEMISTRY 

carbon  atom  which  holds  the  halogen  is  linked  to  two  other  carbon  atoms 
and  in  the  fourth  compound,  which  is  not  normal  but  contains  a 
branched  chain,  the  carbon  atom  which  holds  the  halogen  is  linked  to 
three  other  carbon  atoms.  These  three  different  groupings,  because 
they  are  characterized  by  a  carbon  atom  which  is  linked  to  one,  two 
or  three  other  carbon  atoms,  are  known  as  primary,  secondary  and  ter- 
tiary, and  compounds  containing  such  groups  are  known  as  primary, 
secondary  or  tertiary  compounds.  Denoting  by  R  any  radical  of  one 
or  more  carbon  atoms,  and  by  X  any  substituting  element  or  group, 
we  have  the  three  kinds  of  compounds  represented  by  general  formulas 
as  follows: 


/CH — X    Secondary  Compounds 


R — CH2— X    Primary  Compounds 

R 

R/ 

R\ 

R-^C — X    Tertiary  Compounds 

R/ 

We  shall  find  these  three  classes  of  compounds  of  special  importance 
when  we  study  the  alcohols  in  the  next  chapter.  The  names  of  the 
first,  second  and  fourth  isomeric  butyl  iodides,  as  given  in  the  table  are, 
primary  butyl  iodide,  secondary  butyl  iodide  and  tertiary  butyl  iodide. 
As  the  first  two  are  both  "straight  chain  compounds,  and  the  fourth 
is  a  branched  chain  compound  the  full  names  include  also  the  terms 
normal  or  iso.  The  third  butyl  iodide  is  also  primary,  but  it  is  not 
normal,  therefore  it  is  (primary)  iso-butyl  iodide.  Thus  all  substitu- 
tion products  possess  two  different  characters  depending  upon  their 
structural  or  constitutional  formulas.  One  of  these  characters  depends 
upon  the  nature  of  the  chain  of  carbon  atoms  present ;  if  it  is  a  straight 
chain  it  is  a  normal  compound,  but  if  it  is  a  branched  chain  it  is  an  iso 
compound.  The  other  character  depends  upon  the"  number  of  hydro- 
gens and  of  alkyl  radicals  joined  to  the  carbon  to  which  the  substituting 
group  is  linked.  If  this  carbon  has  two  hydrogens  and  one  alkyl  radi- 
cal joined  to  it,  viz.,  R — CH2 — X,  it  is  known  as  primary.  If  it  has 


ALKYL   HALIDES  49 

R\ 

only  one  hydrogen  and  two  radicals,  viz.,      /CH — X  it  is  secondary, 

W 

R\ 

while  if  it  has  no  hydrogens  and  three  radicals,  viz.,  R — C — X   it   is 

R/ 

tertiary.  Both  of  these  characters  are  always  present  in  any  substitu- 
tion product. 

Official  Names  of  Alkyl  Halides.— The  official  names  of  the  alkyl 
halides  are  derived  in  exactly  the  same  way  as  in  the  case  of  the  hydro- 
carbons. The  number  of  the  carbon  to  which  the  halogen  is  joined, 
together  with  the  name  of  the  halogen,  is  used  as  a  prefix  to  the  official 
name  of  the  hydrocarbon  in  which  the  halogen  is  substituted. 
These  names  are  shown  both  in  the  table  and  in  the  scheme  just 
given. 

Preparation  of  Alkyl  Halides. — We  have  spoken  of  the  formation 
of  the  alkyl  halides  by  the  direct  action  of  the  halogen  upon  the  satu- 
rated hydrocarbon.  In  the  case  of  chlorine  this  action  takes  place  at 
ordinary  temperatures  as  in  the  reaction  between  methane  and  chlorine 
in  the  sunlight.  Bromine,  however,  does  not  act  directly  at  ordinary 
temperatures  but  by  heating  in  a  sealed  tube.  Iodine  does  not  act 
directly  with  the  hydrocarbons.  In  any  case  the  result  is  a  mixture  of 
several  substitution  products,  and  the  method  is  not,  therefore,  of 
practical  value.  Where  direct  action  does  not  occur  the  presence  of 
iodine  chloride  or  antimony  chloride,  which  act  as  carriers,  is  neces- 
sary. The  two  reactions  of  most  importance  in  the  preparation  of 
these  compounds  are  those  involving  either  alcohols  or  unsaturated 
hydrocarbons.  These  will  be  taken  up  when  these  compounds  are 
studied. 

As  in  some  inorganic  compounds  chlorine  replaces  bromine  or  iodine 
and  bromine  replaces  iodine,  so  in  these  alkyl  halides  the  chlorides  may 
sometimes  be  prepared  by  replacing  bromine  or  iodine  with  chlorine, 
and  the  bromide  from  the  iodide  by  means  of  bromine 

R— I  +  Br  R— Br  +  I 

R— I  -f  Cl  — >        R— Cl  +  I 

Alkyl  Halides  as  Synthetic  Reagents. — The  general  reactions  _of 
the  alkyl  halides  are  such  as  result  in  the  replacement  of  the  halogen 


50  ORGANIC  CHEMISTRY 

by  another  radical  or  group.  In  the  Wurtz  and  Frankland  reactions 
for  the  synthesis  of  saturated  hydrocarbons  (p.  16),  two  alkyl  radi- 
cals become  united. 

Alkyl  halide,  R— (I  +  Na2  +  I)— R >R— R  +  2NaI    Hydrocarbon 

Reacting  with  water,  (H — OH),  potassium  hydroxide,  K — OH, 
or  silver  hydroxide,  Ag — OH,  the  radical  will  become  united  to  the 
hydroxyl  group,  (OH). 

Alkyl  halide,  R— (X  +  H)— OH >R— OH  +  H— X  Alkyl  hydroxide 

Alkyl  halide,  R— (X  +  Ag)— OH— ^R— OH  +  Ag—X  Alkyl  hydroxide 

Similarly  with  potassium  cyanide,  K — CN,  and  silver  nitrite,  Ag— 
N02,  compounds  are  obtained  in  which  the  radical  is  united  to  the 
cyanide,  or  to  the  nitro  group. 

Alkyl  halide,  R— (X  +  K)— CN »R— CN  +  K— X  Alkyl  cyanide 

Alkyl  halide,  R— (X  +  Ag)— NO2 >R— N02  +  Ag—X  Nitro  com- 
pound 

With  ammonia  the  ammonia  residue  (— NH2)  becomes  united  to  the 
radical, 

Alkyl  halide,  R— (X  +  H)— NH2 >R— NH2  +  H— X  Alkyl  amine. 

With  nascent  hydrogen  the  alkyl  halides  reform  the  hydrocarbon 
of  the  alkyl  radical. 

Methyl  chloride,  CH3— Cl  +  H2       -»    CH4  +  HC1    Methane. 

The  alkyl  halides  are  therefore  known  as  alkylating  reagents  ,  i.e. 
they  are  used  to  introduce  an  alkyl  radical.  In  this  use  they  are  among 
the  most  important  reagents  in  organic  chemistry  and  are  employed 
in  many  technical  processes. 

In  their  inorganic  compounds  the  three  halogens  chlorine,  bromine 
and  iodine  are  in  this  order  in  regard  to  their  affinity  for  other  elements. 
This  seems  to  hold  also  in  their  organic  compounds  as  shown  by  the 
replacement  of  iodine  by  bromine  or  chlorine,  as  given  previously,  and 
by  the  fact  that  alkyl  iodides  are  the  least  stable  or  the  most  reactive,  while 
the  chlorides  are  the  most  stable  or  the  least  reactive.  This  is  illustrated 
by  their  action  upon  silver  nitrate.  Ethyl  iodide  acts  with  silver 
nitrate  in  alcoholic  solution  precipitating  silver  iodide  even  in  the  cold. 


ALKYL   HALIDES  51 

Ethyl  bromide  precipitates  the  silver  as  bromide  only  on  warming, 
while  ethyl  chloride  does  not  react  with  an  alcoholic  solution  of  silver 
nitrate  at  all.  It  should  be  emphasized  in  this  connection  that  this 
reaction  of  alkyl  halides  and  silver  nitrate  in  alcoholic  solution,  though 
probably  of  the  same  nature  as  that  in  the  case  of  metallic  halides  and 
silver  nitrate  in  water  solution,  is  noticeably  different  in  degree.  This 
is  accounted  for  by  the  fact  that  in  water  both  metallic  halides  and 
silver  nitrate  are  highly  dissociated  into  ions,  whereas  in  alcohol  the 
alkyl  halides  and  silver  nitrate  are  only  very  slightly  dissociated.  As 
alkylating  reagents  the  iodide  is  the  most  important  because  of  its 
greater  activity. 

Properties  and  Uses  of  Alkyl  Halides. — The  alkyl  halides  of  the 
lower  hydrocarbons  are  gases  or  volatile  liquids,  some  of  them  possess- 
ing anesthetic  properties  making  them  valuable  in  medicine.  They 
have  a  sweet  taste,  are  insoluble  in  water,  but  soluble  in  alcohol  and 
ether. 

Methyl  Chloride,  Chlor-methane,  CH3C1,  is  a  gas,  boiling  at  —  237°. 
It  may  be  compressed  in  cylinders  in  which  form  it  is  used  as  a  methy- 
lating  reagent  in  the  manufacture  of  dyes.  It  is  also  used  for  producing 
low  temperatures  and  as  a  local  anesthetic. 

Methyl  iodide,  lodo  methane,  CH3I,  is  a  volatile  liquid,  boiling 
at  42.8°.  Methyl  iodide,  ethyl  iodide  and  ethyl  bromide  are  the  most 
important  of  the  alkyl  halide  reagents. 

Ethyl  chloride,  Chlor-ethane,  CH3— CH2C1,  and  ethyl  bromide, 
brom  ethane,  CH3 — CH2Br,  are  both  used  as  local  anesthetics,  the 
latter  in  dentistry.  The  former  is  a  gas,  boiling  as  12.2°,  which  can  be 
readily  condensed  to  a  liquid  and  is  used  technically  in  this  form. 
Ethyl  bromide  is  a  chloroform-like  liquid  boiling  at  38.4°. 

Ethyl  iodide,  lodo  ethane,  CH3— CH2I 

Propyl  iodide,  i-Iodo  propane,        CH3 — CH2 — CH2 — I 

Iso-propyl  iodide,     2-Iodo  propane,        CH3 — CHI — CHj 


3 


POLY-HALOGEN  COMPOUNDS 


We  have  said  that  substitution  is  the  replacement  of  one  or  more  of 
the  hydrogen  atoms,  in  a  hydrocarbon  or  a  hydrocarbon  radical,  by  an 
equivalent  number  of  other  elements  or  groups  of  elements.  When  one 
monovalent  element  or  group  is  substituted  for  one  hydrogen,  we  have 


52  ORGANIC  CHEMISTRY 

called  the  compounds  mono -substitution  products.  If  two  hydrogens 
are  similarly  substituted  we  term  the  resulting  compounds  di-substitu- 
tion  products.  When  three  are  substituted  we  obtain  tri-substitution 
products,  etc.  The  general  name  for  substitution  products  containing 
more  than  one  substituting  group  is,  poly-substitution  products. 

While  it  is  advisable  to  consider  the  different  groups  of  mono-substi- 
tution products  first  and  by  themselves,  it  is  necessary  to  discuss  briefly  at 
this  time  a  few  facts  in  regard  to  the  poly-halogen  substitution  products 
in  order  that  we  may  understand  a  case  of  isomerism  which  is  essential  in 
establishing  the  constitution  of  aldehydes  and  of  unsaturated  hydrocar- 
bons, both  of  which  are  to  be  studied  before  we  take  up  in  detail  the  full 
discussion  of  poly-substitution  products.  As  we  may  substitute  more 
than  one  monovalent  element  or  group  for  an  equal  number  of  hydrogen 
atoms  these  substituting  elements  or  groups  may  be  the  same  or  may 
be  different.  We  shall  thus  have  compounds  that  will  be  of  mixed 
character.  Also  a  di-valent  element,  e.g.,  oxygen,  may  be  substituted 
for  two  hydrogen  atoms,  etc.  For  our  present  purpose,  however,  we 
shall  confine  ourselves  to  those  compounds  formed  from  the  first  two 
hydrocarbons,  viz.,  methane  and  ethane,  by  the  substitution  of  more 
than  one  halogen  element  of  the  same  kind. 

Poly-halogen  Methanes. — When  methane  is  acted  upon  by  chlo- 
rine or  bromine  directly  a  mixture  of  products  is  obtained  resulting 
from  the  substitution  of  one,  two,  three  or  four  chlorine  or  bromine 
atoms  for  an  equal  number  of  hydrogen  atoms.  The  usual  method  of 
preparing  these  compounds  is  not  by  this  direct  substitution  but  from 
other  compounds  than  the  hydrocarbons  themselves ;  this  will  be  con- 
sidered later  when  we  study  the  compounds  in  detail.  The  four  chlo- 
rine substitution  products  of  methane  which  are  typical  of  all  of  the 
halogen  methanes  have  the  formulas,  CH3C1,  CH2C12,  CHC13  and  CC14, 
and  in  accordance  with  our  ideas  of  the  structure  of  methane,  their 
constitutional  formulas  are, 


H  H  Cl  Cl  Cl 

I  I  I  I  I 

H— C— H  H— C— Cl  H— C— Cl  H— C— Cl  Cl— C— Cl 

I  I  I  I  1 

H  H  H  Cl  Cl 

Methane  Mono-chlor  Di-chlor  Tri-chlor  Tetra-chlor 

methane  methane  methane  methane 


ALKYL   HALIDES 


53 


Only  one  each  of  these  compounds,  or  of  the  other  corresponding  halogen 
compounds,  has  ever  been  prepared  which  has  given  us  our  idea  of  the 
symmetry  of  the  methane  molecule  in  that  all  of  the  hydrogen  atoms  in 
methane  must  be  exactly  alike  so  that  it  makes  no  difference  which  one, 
which  two  or  which  three  are  substituted. 

Poly-halogen  Ethanes. — Just  as  we  may  substitute  more  than 
one  halogen  in  methane  so,  also,  there  are  compounds  known  in  which 
more  than  one  halogen  has  been  substituted  in  ethane.  The  chlorine 
compounds  have  the  formulas:  C2H5C1,  C2H4C12,  C2H3C13,  C2H2C14, 
C2HC15,  C2C16,  and  are  known  respectively  as  mono-,  di-,  tri-,  tetra-, 
penta-,  and  hexa-chlor  ethane. 

Isomerism  of  Di-chlor  Ethanes. — When,  however,  we  study  the 
constitution  of  the  poly-halogen  ethanes  we  find  that  isomerism  occurs 
just  as  in  the  case  of  the  propyl  iodides  and  of  the  hydrocarbons  above 
propane.  In  the  case  of  ethane  it  is  a  fact  that  only  one  mono-substi- 
tution product  of  any  type  is  known,  thereby  proving  the  symmetry  of 
the  ethane  molecule  and  the  like  character  of  all  six  of  the  hydrogen 
atoms.  When  two  hydrogen  atoms  are  substituted  by  two  chlorine 
atoms  two  different  compounds  are  produced  both  having  the  composi- 
tion C2H4C12.  From  the  constitution  of  the  ethane  molecule,  that  has 
been  established  by  its  synthesis  from  methane  (p.  16),  we  can  readily 
see  how  this  may  be  explained  as  we  may  have  two  hydrogen  atoms 
replaced  by  two  chlorine  atoms  in  two  different  ways,  as  follows: 

CH3— CH3  CH3— CHC12  CH2C1— CH2C1 

H    H  H    H  H    H 

II  II  II 

H— C— C— H  H— C— C— Cl  Cl— C— C— Cl 

II  II  II 

H    H  H    Cl  H    H 

Ethane  Unsymmetrical  Symmetrical 

di-chlor  ethane  di-chlor 

ethane 

The  fact  that  two  compounds  exist  of  the  formula  (C2H4C12)  means  that 
these  two  structural  formulas  must  represent  different  substances. 
Our  ideas  and  the  facts  are  thus  in  agreement.  Although  all  six  of  the 
hydrogens  are  alike,  and  it  makes  no  difference  which  one  of  the  six 
is  substituted  by  chlorine,  as  proven  by  the  existence  of  only  one  mono- 


54  ORGANIC  CHEMISTRY 

chlor  ethane,  yet  when  we  replace  two  hydrogen  atoms  in  ethane  by 
two  chlorine  atoms,  two  compounds  are  possible;  as  in  one  case  both 
chlorine  atoms  are  linked  to  the  same  carbon  atom,  while  in  the  other 
they  are  each  linked  to  a  different  carbon  atom.  One  of  the  compounds, 
CH2C1 — CH2C1,  is  termed  symmetrical  di-chlor  ethane,  the  other 
CH3 — CHC12,  unsymmetrical  di-chlor  ethane.  This  isomerism  of  the 
symmetrical  and  unsymmetrical  di-substitution  products  of  ethane  is 
the  important  fact  to  be  remembered  later  on. 

(B)  MONO-AMINO  SUBSTITUTION  PRODUCTS 
ALKYL  AMINES     R-NH2     AM1NO  ALKANES 

Synthesis. — We  have  shown  that  the  alkyl  halides  are  mono-sub- 
stitution products  of  the  hydrocarbons,  i.e.,  one  hydrogen  of  the  hydro- 
carbon has  been  substituted  by  a  halogen,  e.g.,  methyl  iodide,  CH3 — I. 
Now  when  methyl  iodide  is  treated  with  ammonia  a  new  compound  is 
formed  having  the  composition  CH5N  and  the  other  product  of  the 
reaction  is  hydrogen  iodide, 

Amines. — This  compound  and  similar  ones  derived  from  other  hy- 
drocarbons are  known  as  amines,  and  were  first  discovered  by  Wurtz  in 
1848.  Hofmann,  in  1850,  showed  conclusively  that  these  nitrogen  con- 
taining compounds  are  to  be  considered  as  derivatives  of  ammonia  in 
which  the  monovalent  nitrogen  radical  ( — NH2),  a  residue  of  ammonia, 
is  linked  to  an  alkyl  radical.  Methyl  iodide  is  made  up  of  the  methyl 
radical  linked  to  iodine  and  in  the  above  reaction  the  iodine  leaves  the 
methyl  and  unites  with  one  hydrogen  from  the  ammonia,  the  place  of 
the  iodine  being  taken  by  the  residue  of  the  ammonia  ( — NH2).  The 
reaction  becomes  then: 

CH3— (I    +   H)— NH2        >        CH3— NH2    +    H— I 

Methyl  iodide  Methyl  amine 

As  it  is  derived  from  ammonia  the  group  ( — NH2),  is  given  the  name  of 
the  amino  radical.  It  has  never  been  isolated,  and  we  do  not  know  it 
as  a  free  substance  nor,  as  has  been  stated,  do  we  know  the  radical 
(CH3 — )  as  a  free  substance. 

Amino  Compounds. — We  have  previously  explained  how  mono- 
chlof  methane,  i.e.,  methane  in  which  one  hydrogen  atom  has  been  sub- 
stituted by  a  chlorine  atom,  may  with  equal  justice  be  considered 


ALKYL    AMINES  55 

as  methyl  chloride,  i.e.,  hydrogen  chloride  in  which  the  hydrogen  atom 
has  been  substituted  by  the  methyl  radical. 

In  the  same  way  we  may  consider  these  new  compounds  either  as 
amino  substitution  products  of  the  hydrocarbons  or  as  alkyl  substitution 
products  of  ammonia. 

H  H 

I  i 

H— C— (I  +  H)— NH2  ->        HI  +  H— C— NH2        or 

Ammonia 

H  H 

lodo  methane  Amino 

methane 

/(H  /CH3 

Ne  H  -f  I)— CH3  — >        HI  +  N^-H 

\  TT  Methyl  \TT 

iodide 

Ammonia  Methyl 

amine 

If  we  consider  them  as  substituted  hydrocarbons  they  are  known  as 
amino  or  amido  substitution  products,  e.g.,  amino  methane.  If  they 
are  considered  as  ammonia  in  which  the  alkyl  group  has  been  sub- 
stituted, they  are  called  substituted  ammonias  or  amines,  e.g.,  methyl 
amine. 

Basic  Character. — The  alkyl  amines  then  are  analogous  to  alkyl 
halides,  and  we  find  a  corresponding  homologous  series,  e.g.,  methyl 
amine,  ethyl  amine,  propyl  amine,  etc.  They  are  strongly  basic  com- 
pounds, in  fact,  they  are  of  especial  interest  because  they  are  more 
strongly  basic  than  the  ammonia  from  which  they  are  derived. 

The  characteristic  properties  and  reactions  of  ammonia  are  also  true 
of  the  amines.  They  have  a  strong  fishy,  ammonia-like  odor,  but  unlike 
ammonia  the  lower  ones  are  inflammable.  It  was  this  fact  which  led 
to  their  discovery.  Wurtz  supposed  that  the  volatile  substance  he  had 
obtained  was  ammonia  until  a  flame  was  accidentally  brought  near  it 
when  it  ignited.  They  are  readily  soluble  in  water,  and  their  solutions 
are  alkaline  to  litmus. 

Salts. — When  ammonia  reacts  with  an  acid,  e.g.,  hydrochloric  or 
hydriodic  acid,  there  is  formed  an  addition  product  or  salt  in  which  the 
trivalent  nitrogen  of  ammonia  is  converted  into  the  pentavalent  nitrogen 


ORGANIC  CHEMISTRY 


of  the  ammonium  salt.     In  the  same  way  when  methyl  amine  reacts 
with  hydriodic  acid  a  salt  of  the  amine  is  obtained. 


N^H    +    HI 
XH 

Ammonia 


N 


H 
H 

H  and  N; 

H 

I 


CH; 

H 

H 

H 

I 


Ammonium 
iodide 


Methyl 

ammonium 

iodide 


CH 


H 


Methyl 
amine 


HI 


The  compound  formed  from  the  amine  is  a  substituted  ammonium  salt, 
viz.,  methyl  ammonium  iodide.  It  is>nown  more  generally,  however, 
as  methyl  amine  hydriodide,  and  is  usually  written,  CH3 — NH2 — HI. 
When  this  salt  is  treated  with  a  stronger  base,  e.g.,  sodium  hydroxide, 
the  amine  is  again  formed  just  as  ammonia,  NH3,  is  set  free  from  its 
salts  by  the  same  reagent. 


H 

H 

H  +  NaOH 

H 

I 


Nal 


H 
H 

N^  -H 


Ammonium 
iodide 


CH3 

H 

H     +     NaOH 

H 


Ammonium 
hydroxide 
(unstable) 


Nal     +     N; 


NH  +  H— OH 
XH 

Ammonia 


CH3 
H 
-H        — 


Methyl 

ammonium 
iodide 


Methyl  ammonium 
hydroxide  (unstable) 


/CH3 

N^H     +     H—  OH 
XH 

Methyl 
amine 


In  the  reaction  previously  given  for  the  synthesis  of  the  amines  from 
the  alkyl  halides  the  salts  of  the  amines  are,  in  fact,  formed  as  the 


ALKYL   AMINES 


57 


result  of  a  secondary  reaction  between  the  amine  and  the  halogen  acid, 
the  complete  reaction  being 


H 

Ammonia 


[— CH3 

Methyl 
iodide 


rf-H    +    HI 


N 


Methyl 
amine 


CH3 

H 

H 

H 

I 

Methyl  ammonium 
iodide 


Primary,  Secondary  and  Tertiary  Amines. — The  amines  that  we 
have  considered,  which  are  formed  from  ammonia  by  the  replacement 
of  one  hydrogen  by  one  alkyl  radical,  are  termed  primary  amines.  They 
not  only  act  like  ammonia  in  the  ways  just  mentioned,  but  they  react 
with  alkyl  halides  just  as  ammonia  itself  does  and  a  second  hydrogen 
united  to  nitrogen  is  replaced  by  methyl. 


CH; 


CH 


TT 

Methyl 
amine 


I)—  CH8 

Methyl 
iodide 


+      HI 


N; 


H 

Di-methyl 
amine 


H 
H 
I 

Di-methyl 

ammonium 

iodide 


Such  an  amine  resulting  from  the  replacement  of  two  of  the  ammonia 
hydrogens  by  two  methyl  or  other  hydrocarbon  radicals  is  known  as  a 
di-amine  or  a  secondary  amine.  These  di-amines  likewise  react  with 
alkyl  halides  in  the  same  way  and  the  third  ammonia  hydrogen  is 
replaced  by  a  radical  as  follows: 

CH3 
CH3 
CH3 

TT 
I 


CH3 


X(H 

Di-methyl 
amine 


I)-CH3 

Methyl 
iodide 


XC 


+      HI 


H3 

Tri-methyl 
amine 


Tri- methyl 

ammonium 

iodide 


An  amine  thus  related  to  ammonia  in  that  all  three  of  the  ammonia 
hydrogens  are  replaced  by  hydrocarbon  radicals  is  called  a  tri-amine 
or  a  tertiary  amine. 


58  ORGANIC  CHEMISTRY 

Tetra-methyl  Ammonium  Salts. — Not  only  do  these  tri-amines 
unite  directly  with  the  hydrogen  halides  forming  ammonium  salts  as 
above,  but,  being  much  more  strongly  basic  than  the  mono-ordi-amines. 
they  unite  also  with  the  alkyl  halides  themselves  forming  salts  of 
similar  character.  Thus: 


CH3 

+  I—  CH3  -*  N<-CH 

Methyl  iodide  \\CH3 

Tri-methyl^amine  \j 

Tetra-methyl  ammonium 
iodide 


These  salts  are  known  as  tetra-methyl  ammonium  salts  or  quaternary 
compounds. 

When  the  methyl  ammonium  salts  of  the  hydrogen  halogen  acids 
are  decomposed  by  sodium  hydroxide  there  is  probably  first  formed  an 
ammonium  hydroxide-like  compound  just  as  in  the  case  of  ammonium 
salts  themselves.  These  hydroxide  compounds,  like  ammonium  hy- 
droxide, are  not  possible  of  isolation,  but  decompose  as  was  represented 
in  the  reaction  as  just  given  for  setting  free  the  methyl  amine  from  its 
hydriodide  salt.  With  the  tetra-methyl  ammonium  salts,  however, 
sodium  hydroxide  does  not  set  free  the  tri-methyl  amine,  and  if  we  use 
silver  hydroxide  (moist  silver  oxide)  instead  of  sodium  hydroxide,  silver 
iodide  is  formed  and  the  hydroxide  of  the  tetra-methyl  ammonium  salt 
is  set  free.  By  heating,  this  decomposes,  methyl  alcohol  being  one  of 
the  products  and  tri-methyl  amine  the  other.  All  of  the  products  are 
thus  the  methyl  analogues  of  ammonia  compounds  and  water.  Writing 
the  two  sets  of  reactions  together  makes  this  plain. 

/H  /H 

AH  //-H  H 

-  >    Nal  +  N^  —  H    -  >    NeH  +  H—  OH 


H\TT  Water 

Hydrogen 
Ammonia        hydroxide 


,OH 

Ammonium  Ammonium 

iodide  hydroxide 

(unstable) 


ALKYL   AMINES  59 

/CH3  CH3 

///CH3 
N-  —  CH3  -f  Ag)OH  -» 


(I  OH 

Tetra-methyl  Tetra-methyl 

ammonium  ammonium 

iodide  hydroxide 

(stable) 


CH3—  OH 

Methyl 
alcohol 
Tri-methyl  Methyl 

amine  hydroxide 

The  salts  of  the  amines  and  halogen  acids  are  all  crystalline  compounds 
soluble  in  water  and  similar  to  ammonium  salts  in  every  respect.  The 
only  hydroxide  compound  which  can  be  isolated  is  the  tetra-methyl 
ammonium  compound  which  is  stable  at  ordinary  temperatures  and 
decomposes  only  on  heating.  The  reason  for  this  is  undoubtedly  in 
the  fact  that  all  of  the  other  hydroxides,  those  formed  from  the  pri- 
mary, secondary  and  tertiary  amine  salts,  have  at  least  one  hydrogen 
left  in  union  with  the  nitrogen,  and  this  hydrogen  always  breaks  off 
with  the  hydroxyl  forming  water,  and  the  amine  is  left  free.  In  the 
tetra-methyl  ammonium  hydroxide  there  is  no  hydrogen  left  united  to 
the  nitrogen  and,  therefore,  water  cannot  split  off.  Tetra-methyl 
ammonium  hydroxide  is  a  crystalline  substance  possessing  strong  basic, 
even  caustic,  properties  and  absorbs  water  and  carbon  dioxide  readily 
from  the  air.  The  fact  that  this  compound  exists  as  a  stable  compound 
gives  support  to  the  belief  that  the  corresponding  hydrogen  compound, 
viz.,  ammonium  hydroxide,  which  is  so  unstable  that  it  does  not  exist 
under  ordinary  conditions,  is  nevertheless  a  definite  compound  pos- 
sible of  existence  under  conditions  which  have  not  been  attained. 

Distinction  Between  Primary,  Secondary  and  Tertiary  .Amines. 
When  an  alkyl  halide  and  ammonia  react  the  reaction  is  not  a  clean 
cut  one  by  which  either  a  primary,  a  secondary,  a  tertiary  or  a  quater- 
nary amine  or  amine  salt  is  formed.  By  regulating  the  conditions  of 
the  reaction  the  product  may  have  one  of  these  in  the  greatest  amount, 
but  it  always  contains  a  mixture  of  all  of  the  salts.  The  separation  of 
the  amines  from  each  other  or  the  distinguishing  of  one  from  the  others 
is,  therefore,  important.  As  one  of  the  reactions  on  which  such  a  sepa- 


60  ORGANIC  CHEMISTRY 

ration  is  based  involves  the  iso-nitriles,  a  class  of  compounds  we  have 
not  yet  studied,  the  discussion  of  this  particular  reaction  will  be  de- 
ferred until  later. 

Nitrous  Acid  and  Amines.  —  The  other  method  of  distinction  depends 
upon  the  action  of  nitrous  acid  on  the  amines.  When  a  primary  amine 
reacts,  with  nitrous  acid,  HNO2  or  HO  —  NO,  a  salt  of  the  amine  is 
formed  exactly  similar  to  the  hydrochloride  salt. 

Primary  Amines,  Salts  of  Nitrous  Acid 

R—  NH2  +  HNO2        -  >        R—  NH2—  HNO2      or 

Alkyl  amine  Alkyl  ammonium  nitrite 


H  +  HNO2  -»         N      -H 

XH 


This  compound  is  analogous  to  ammonium  nitrite  and  decomposes 
readily  just  as  ammonium  nitrite  does.  Ammonium  nitrite  yields 
water  while  the  alkyl  ammonium  nitrite  yields  alcohol  and  water,  the 
nitrogen  being  set  free  in  both  cases. 

H  /R 

H  /H 

2H2O  +  N2    <—    N-  —  H        N-  -H  -  >  N2  +  H2O  +  R—  OH 

Water  \\TT  \\    TJ  Alcohol 


\NO2  \NO2 

Ammonium         Alkyl  ammonium 
nitrite  nitrite 

The  entire  reaction  of  the  primary  amine  may  be  written  in  other  ways 
as  follows: 

R—  (N)  =  H2 
R—  |N(H2  +  0)N—  |OH  -  >R—  OH  +  N2  +  H20<—  + 

Primary  Nitrous  acid  Alcohol  Tjr\       f\J\  —  C\ 

amine  *1U       ^1\  )  —\J 


Primary  amine 
+  Nitrous  acid 


This  shows  that  the  reaction  depends  upon  the  two  remaining  ammonia 
hydrogens  which  unite  with  the  non-hydroxyl  oxygen  of  the  nitrous 
acid  forming  water,  leaving  the  hydroxyl  group  of  the  nitrous  acid  for 
the  alkyl  radical.  We  shall  find  when  we  study  the  primary  amines 


ALKYL   AMINES  6 1 

of  the  benzene  series  in  Part  II,  that  while  the  end  products  of  the 
two  reactions  are  of  the  same  kind  the  benzene  compounds  do  not  form 
salts  with  nitrous  acid,  because  they  are  less  strongly  basic.  In  this 
case,  however,  a  most  interesting  class  of  intermediate  products  is 
formed  which  is  not  produced  with  the  alkyl  amines. 

Secondary  Amines,  Nitroso  Amines. — When  a  secondary  amine  re- 
acts with  nitrous  acid  the  reaction  is  entirely  different.  A  compound 
containing  the  group  ( — NO) ,  in  place  of  the  one  hydrogen  of  the  amine 
and  known  as  a  nitroso  amine,  is  formed. 


+  H20 
H  +  HO)NO  NO 

Di-methyl  Di-methyl 

amine  nitroso  amine 

In  the  secondary  amine  there  are  not  two  remaining  ammonia  hydro- 
gens and  the  reaction  cannot  take  place  as  with  primary  amines.  In- 
stead, the  one  remaining  ammonia  hydrogen  unites  with  the  hydroxyl 
of  the  nitrous  acid  forming  water,  and  the  other  product  is  the  nitroso 
amine.  These  nitroso  compounds  are  able  to  be  distilled  and  can  be 
reconverted  into  the  amine  by  means  of  hydrochloric  acid. 

Tertiary  Amines.  —  In  the  tertiary  amines  there  is  no  remaining 
ammonia  hydrogen,  therefore,  neither  the  primary  nor  secondary  amine 
reactions  can  take  place.  The  fact  is  that  tertiary  amines  do  not  re- 
act with  nitrous  acid  at  all.  We  thus  have  a  reaction  which  enables 
us  to  distinguish  between  primary,  secondary  and  tertiary  amines. 
Writing  these  reactions  together  we  have 

R—  [N(H2  +  0)N]—  OH       -  >       R—  OH    +   N2  +  H2O 

Primary  amine  Alkyl  hydroxide 

N  R\ 

)N(H  +  HO)—  NO  —  >  >N—  NO    +  H2O 

W  K 

Secondary  amine  Nitroso  amine 

N 

RN    +    HO—  NO  —  >        Do  not  react 


Tertiary 
amine 


Isomerism.  —  The  isomerism  of  the  amines  may  be  due  to  several 
things.     First,  it  may  be  due  to  isomerism  of  the  alkyl  radical,  and  as 


62 


ORGANIC  CHEMISTRY 


such  will  be  of  the  same  nature  as  the  isomerism  of  the  alkyl  halides, 
e.g.,  C3H9Nniaybe 

CH, 


/CH2 — CH2 — CH; 


CH—  CH, 


Propyl  amine 
i-Amino  propane 


Iso-propyl  amine 
2-Amino  propane 


Such  isomerism  is  possible  in  all  three  classes  of  amines.  Second,  it 
may  be  due  to  different  alkyl  groups  whereby  primary,  secondary 
and  tertiary  amines  become  isomeric  with  each  other,  e.g.,  the  same 
empirical  formula,  C3H9N  may  be: 


/CH 


N; 


Propyl  amine 
Primary 


H 

Methyl  ethyl  amine 
Secondary 


-CH3 
CH3 
CH3 


Tri-methyl  amine 
Tertiary 


We  thus  have  four  isomeric  amines  of  the  formula  C3H9N. 


TABLE  VI11. — HOMOLOGOUS  SERIES  OF  ALKYL  AMINES 


Alkyl  radical 

Primary  R-NH2 

Secondary  R^NH 

R\ 
Tertiary  R—  N 
R/ 

B.P. 

B.P. 

B.P. 

Methyl  

-    6° 

'        +  7° 

+  3-5° 

Ethyl.  . 

+  IQ° 

56* 

00° 

Propvl  . 

40° 

Q8° 

156° 

Iso-proDvl 

,2° 

84° 

Ethyl  methyl  

is* 

Hepta-decyl(C17H35)  
Triacontyl  (C30H6i)  

340° 
M.P.  49° 

M.P.  78° 

The  highest  members  given  are  the  highest  known,  and  it  will  be 
noticed  that  they  are  solids.  They  are  also  insoluble  in  water,  and  are 
less  basic  and  not  like  ammonia  in  their  physical  properties  as  are  the 
lower  members. 


HYDROXYLAMINE,    HYDRAZINE,    HYDR  AZOIC   ACID  63 

Methyl  Amines 

All  three  of  the  methyl  amines  are  found  naturally  in  herring  brine, 
and  in  the  dry  distillation  products  of  the  residues  obtained  from  fer- 
mented beet  sugar  molasses  after  it  has  been  evaporated  to  drive  off 
the  alcohol  and  water.  They  also  occur  in  certain  plants  and  as 
the  decomposition  products  of  more  complex  nitrogenous  organic  sub- 
stances such  as  morphine. 

Hydroxylamine,  Hydrazine,  Hydrazoic  Acid 

Three  compounds  will  now  be  given,  two  of  which  are  closely  re- 
lated to  the  amines  in  that  they  are  the  simplest  derivatives  of  ammonia 
which  we  know. 

Hydroxyl  Amine.  —  The  first  compound  is  an  ammonia  derivative, 
and  is  known  as  hydroxyl  amine.  When  nitric  acid  is  reduced  by  nas- 
cent hydrogen  a  compound  is  obtained,  the  composition  of  which  is 
NH3O  and  which  proves  to  be  a  hydroxyl  substitution  product  of 
ammonia,  NH2  —  OH  or  hydroxyl  amine.  It  may  be  looked  upon  as 
ammonia  in  which  one  hydrogen  has  been  oxidized  to  hydroxyl.  It 
thus  stands  between  nitric  acid  and  ammonia  which  are  reciprocal 
oxidation  and  reduction  products. 

/H  +0  /OH  +30  /OH 

N^H        t  N^-H  :  ---  "        N=O         +      H20 

XH  H2+  XH  3H2+  X) 

Ammonia  Hydroxyl  amine  Nitric  acid 

Hydroxyl  amine  is  a  hygroscopic  liquid,  readily  soluble  in  water  and 
possesses  the  basic  and  salt-forming  properties  of  ammonia. 


/OH  /H 

N^H         +        HC1         —  »      N-  -H 
XH  ^H 

Hydroxyl  amine  \/~*1 

(base)  yl 

Hydroxyl  amine 
hydrochloride  (salt) 

The  salts  are  crystalline,  soluble  compounds.  Hydroxyl  amine  is  of 
especial  importance  in  connection  with  the  study  of  aldehydes,  and  will 
be  mentioned  again  at.  that  time. 


64  ORGANIC  CHEMISTRY 

Hydrazine. — The  second  compound  is  known  as  hydrazine,  and 
is  obtained  by  oxidizing  urea  or  by  reducing  hyponitrous  acid.  It 
has  the  composition  N2H4,  and  is  one  of  two  compounds,  other  than 
ammonia,  which  contains  simply  nitrogen  and  hydrogen.  It  forms  de- 
rivatives which  prove  it  to  be  represented  by  the  formula  H2N — NH2 
which  might  also  be  called  di-amine  or  di-amide;  It  was  discovered  in 
1887  by  Curtius.  It  may  be  looked  upon  as  an  amine  substitution 
product  of  ammonia.  It  is  similar  to  ammonia  in  its  basic  character 
and  in  its  formation  of  a  hydroxide  base  and  salts.  It  is  a  crystalline 
compound,  m.p.  — 1°  and  is  soluble  in  water.  Its  derivatives,  formed 
by  replacing  one  or  more  hydrogens  by  alkyl  or  other  hydrocarbon 
radicals,  are  the  important  compounds.  Phenyl  hydrazine,  C6H5— 
NH— NH2,  is  a  derivative  containing  a  hydrocarbon  radical  of  the 
carbo-cyclic  series  of  compounds  known  as  phenyl,  (C6Ho — ).  The  im- 
portance of  this  compound,  as  of  hydroxyl  amine,  will  be  seen  when  we 
study  the  aldehydes,  and  the  sugars.  Di-methyl  hydrazine,  (CH3)2N— 
NH2  may  also  be  mentioned. 

Hydrazoic  Acid. — The  third  compound,  which  is  the  other  one 
containing  only  nitrogen  and  hydrogen,  is  not  an  ammonia  deriva- 
tive. It  is  known  as  hydrazoic  acid  or  tri-azoic  acid.  Its  formula  is 
N3H.  It  is  a  mono-basic  acid  while  ammonia,  NH3,  is  a  base.  It 
forms  a  salt  with  ammonia,  NH4N3,  ammonium  hydrazoate.  Hy- 
drazoic acid  was  also  discovered  by  Curtius  in  1890. 


(C)  PHOSPHORUS  AND  ARSENIC  COMPOUNDS 
I.  PHOSPHINES    R— PH2 

Phosphina,  Phosphonium  Salts. — It  will  be  recalled  from  our  study 
of  inorganic  chemistry  that  phosphorus  forms  a  compound  with 
hydrogen  analogous  to  the  nitrogen  and  hydrogen  compound  am- 
monia, NH3.  It  is  given  the  formula  in  the  gaseous  state  of  PH3, 
and  is  called  phosphine.  This  compound  like  ammonia  forms  salts 
with  acids  that  are  known  as  phosphonium  salts. 

PH3      +      HI        >        PH4I 

Phosphine  Phosphonium  iodide 


.       PHOSPHINES    AND    ARSINES  65 

Alkyl  Phosphines  and  Phosphonium  Compounds.  —  The  simpler 
organic  compounds  of  phosphorus  are  alkyl  phosphines  exactly  analo- 
gous to  the  amines. 


H          or      H—  PH2  Phosphine 

H 


H          or      CH3—  PH2  Primary  alkyl  phosphine 

H 

CH3 

CH3      or      (CH3)  2  =  PH        Secondary  alkyl  phosphine 

H 

CH3 

CH3      or      (CH3)3  =  P  Tertiary  alkyl  phosphine 

CH3 

/CH3 

/CH3 

—  CH3  or  (CH3)4  =  P  —  I        Quaternary  alkyl  phosphonium  iodide 


CH3 


P^—  CH3  or  (CH3)4  =  P — OH  Quaternary  phosphonium  hydroxide 
^  CHz  (base) 

XOH 

The  primary,  secondary  and  tertiary  phosphines  are  weak  bases, 
stronger,  however,  than  the  phosphine  itself  which  is  scarcely  basic  at 
all.  The  tetra-alkyl  phosphonium  hydroxides  are  strong  bases. 

II.  ARSINES    R— AsH2 

Corresponding  arsenic  compounds  in  which  arsenic  is  united  to 
alkyl  radicals  are  derived  from  arsine,  AsH3.  The  primary  and 
secondary  alkyl  arsines  are  not  known  except  as  chlorine  or  oxygen 

5 


66  ORGANIC  CHEMISTRY 

derivatives.  The  tertiary  alkyl  arsines,  however,  are  strong  bases 
forming  salts  analogous  to  the  quaternary  alkyl  ammonium  salts. 

XCH3 

/>CH3 

(CH3)3^As  — »        (CH3)4=As— OH         or         As^— ~CH3 

Tri-methyi  arsine  Tetra-methyl  ^\  p-rr 

arsonium  \     ^**l 

hydroxide  \  /-\TT 

These   arsenic   compounds   are   known   as  cacodyl  compounds.     The 

//-^TT    V  \ 

radical  (        3  yAs — • )  was  called  cacodyl  by  Bunsen  who  discovered  it 

in  1859.  It  was  given  this  name  from  cacodus,  stinking,  because  com- 
pounds containing  it  possess  an  extremely  bad  odor.  The  oxygen 
derivatives  of  the  methyl  arsines  are  of  especial  interest  because  they 
were  among  the  important  compounds  studied  in  the  development  of 
the  radical  theory.  The  cyanogen  radical  of  Gay  Lussac,  the  benzoyl 
radical  of  Liebig  and  Wohler,  and  the  cacodyl  radical  of  Bunsen  are 
always  thought  of  in  connection  with  the  radical  theory. 

D.  MONO-CYANOGEN  SUBSTITUTION  PRODUCTS 
I.  ALKYL  CYANIDES     R— CN     ACID  N1TRILES 

The  next  class  of  substitution  products  of  the  saturated  hydrocar- 
bons which  we  shall  study  are  those  formed  from  the  alkyl  halides  by 
the  action  of  potassium  cyanide  or  silver  cyanide. 

Acids  and  Salts  of  Cyanogen. — We  have  been  accustomed  in  inorganic 
chemistry  to  the  group  (CN)  known  as  the  cyanide  or  cyanogen  group. 
The  compounds  which  are  generally  treated  as  inorganic  are  hydrogen 
cyanide  or  hydrocyanic  acid,  HCN;  metal  salts  of  this  acid,  the  metal 
cyanides,  e.g.,  potassium  cyanide,  KCN,  silver  cyanide,  Ag(CN), 
mercuric  cyanide,  Hg(CN)2,  ferrous  and  ferric  cyanides.  Fe"(CN)2 
and  Fe'"(CN)3;  the  double  salts  of  potassium  and  iron,  potassium  fer- 
rocyanide,  K4Fe"(CN)6  or  4KCN.Fe"(CN)2  and  potassium  fern- 
cyanide,  K3Fe'"(CN)6  or  3KCN.Fe'"(CN)3  and  finally  the  double 
salts  of  iron,  corresponding  to  these  potassium  salts  just  given,  e.g., 
ferric  ferrocyanide,  Fe'"4(Fe"(CN)6)3  or  4Fe'"(CN)3.  3Fe"(CN)2, 
which  is  known  as  Prussian  Blue,  and  ferrous  ferri-cyanide  Fe'V 
(Fe"'(CN)6)2  or  3Fe"(CN)2.2Fe'"(CN)3  known  as  TurnbulPs  Blue. 


ALKYL  CYANOGEN  COMPOUNDS  67 

These  iron  double  salts  are  mostly  blue  in  color,  and  it  is  from  this 
fact  that  the  group  (CN)  receives  its  name  of  cyanogen  from  the 
Greek  word  cyanos  meaning  blue.  Hydrocyanic  acid  and  the  simple 
cyanide  salts  are  analogous  to  the  halogen  binary  acids  and  salts,  and 
when  oxidized  they  yield  an  oxygen  acid  and  salts  analogous  to  the 
oxygen  containing  chlorine  compounds. 

Acid  Salt  Oxidized  Acid  Oxidized  Salt 

HC1  KC1  HOC1  KOC1 

Hydrochloric  acid         Potassium  chloride  Hypochlorus  Potassium 

acid  hypo- 

chlorite 

H(CN)  K(CN)  HO(CN)  KO(CN) 

Hydro  cyanic  acid        Potassium  cyanide  Cyanic  acid  Potassium  cyanate 

(unknown) 

Relation  to  Organic  Compounds.— It  is  a  striking  fact  that  whenever 
an  organic  animal  or  vegetable  substance  containing  nitrogen  is  heated 
with  metallic  sodium  the  sodium  compound  of  cyanogen  is  formed. 
There  is  no  reason  for  supposing  that  all  such  organic  nitrogen  is  present 
in  the  form  of  the  cyanogen  grouping  but  simply  that  on  decomposi- 
tion, under  these  conditions,  nitrogen  and  carbon  leave  the  compound, 
combined  in  this  way.  This  reaction  is  used  as  a  test  for  nitrogen  in 
protein  substances  and  may  easily  be  made  with  such  material  as  hair, 
gelatin,  egg  albumin,  etc.  It  is  also  the  basis  of  the  commercial  method 
for  making  potassium  ferrocyanide,  K4Fe(CN)6,  which  is  prepared  by 
heating  substances  containing  nitrogen,  e.g.,  animal  matter  such  as 
blood,  etc.,  together  with  iron  filings  and  potassium  carbonate. 

Protein  Compounds  (C.H.O.N.)  +  Fe  -f-  K2C03       — >    K4Fe(CN)6 

Potassium  ferrocyanide  by  heating  with  K^COs  is  converted  into 
potassium  cyanide,  KCN,  and  potassium  cyanate,  KOCN,  and  by 
oxidation  with  bromine  or  potassium  bichromate  yields  potassium 
ferricyanide,  K3Fe(CN)6.  It  is  thus  the  starting  point  for  all  of  the 
cyanogen  compounds. 

Whether  the  true  place  to  study  these  compounds  is  in  organic  or 
inorganic  chemistry  will  not  be  considered.  As  they  have  probably 
been  taken  up  in  connection  with  inorganic  qualitative  analysis  they 
will  simply  be  mentioned  in  order  to  introduce  the  alkyl  cyanogen 
compounds  which  we  shall  now  study.  Later,  however,  all  of  the  above 
mentioned  cyanogen  compounds  together  with  sulphur  analogues  will 
be  discussed  in  detail  (p.  408). 


68  ORGANIC  CHEMISTRY 

Free  Cyanogen. — When  mercuric  oxide  is  heated,  oxygen  is  set  free 
as  a  gas  and  metallic  mercury  is  left.  A  similar  change  occurs  when 
mercuric  cyanide  is  heated.  Mercury  is  left  and  a  gas  is  given  off 
which  is  extremely  poisonous,  colorless,  soluble  in  water,  and  which 
burns  with  a  blue  flame.  This  substance  is  known  as  cyanogen  and 
has  the  composition  (CN)2. 

2HgO    >     2Hg    +     02     |     (CN)2     +     Hg    <-       Hg(CN)2 

Mercuric  Mercury         Oxygen  ;     Cyanogen  Mercury  Mercuric 

oxide  cyanide 

Cyanogen  Radical. — As  stated  at  the  beginning  of  this  chapter, 
cyanogen  substitution  products  of  the  hydrocarbons  are  formed  when 
alkyl  halides  are  treated  with  potassium  cyanide.  These  compounds 
contain  cyanogen  as  a  substituting  group  or  radical  analogous  to  the 
halogen  elements,  and  the  radicals,  methyl  (CH3)  amino  (NH2),  hy- 
droxyl  (OH),  etc.  A  striking  difference  between  the  radical  cyano- 
gen and  the  methyl,  amino  and  hydroxyl  radicals  is  that  the  cyanogeji 
radical  is  known  in  the  free  condition.  The  free  substance,  the  gas 
cyanogen,  probably  bears  the  same  relation  to  the  radical  cyanogen 
that  a  molecule  of  oxygen  does  to  the  atom. 

Methyl  Cyanide     CH3— CN     Cyano  Methane 

When  methyl  iodide  is  treated  with  potassium  cyanide  a  compound 
with  the  composition  C2H3N  is  formed  by  a  simple  reaction  of  metathe- 
sis. As  this  and  many  other  reactions  prove  that  both  the  methyl  and 
the  cyanogen  radicals  are  present  in  the  compound  we  express  the 
reaction, 

CH3— (I  +  K)— CN        >        CH3— CN  +  KI 

Methyl  iodide  Methyl  cyanide 

Carbon  Linked  to  Carbon. — Do  we  know,  however,  that  the  cyano- 
gen carbon  is  linked  to  the  methyl  carbon  or  is  the  nitrogen  the  linking 
atom?  When  methyl  cyanide  is  boiled  with  water  or  alkalies  acetic 
acid  and  ammonia  are  formed.  In  acetic  acid,  as  we  shall  show  later, 
there  are  two  carbon  atoms,  the  same  as  in  methyl  cyanide,  and  the 
two  carbons  are  linked  together.  Therefore,  in  methyl  cyanide  the 
cyanogen  carbon  is  linked  directly  to  the  methyl  carbon. 

CH3— CN     +     2HOH      >       CH3— COOH     +     NH3 

Methyl  cyanide  Acetic  acid  Ammonia 


ALKYL  CYANOGEN  COMPOUNDS  69 

Acid  Nitriles. — This  is  a  general  reaction  of  alkyl  cyanides  or  of 
any  similar  cyanogen  substitution  product  so  that  whenever  organic 
acids  containing  the  same  number  of  carbon  atoms  are  formed  from  cy- 
anogen compounds  we  know  that  the  carbon  of  the  cyanogen  and  not 
the  nitrogen  is  the  joining  link.  Because  of  this  definite  relation  to 
acids  the  cyanides  are  known  also  and  more  generally  as  acid  nitriles. 

Relation  to  Amines. — When  the  alkyl  cyanides  are  treated  with 
nascent  hydrogen  an  alkyl  amine  is  formed  in  which  the  alkyl^  radical 
has  one  carbon  more  than  the  alkyl  radical  of  the  cyanide. 

CH3— CN  +  2H2        >        CH3— CH2— NH2 

Methyl  Ethyl  amine 

cyanide 

This  is  a  general  method  for  preparing  amines,  and  affords  another  proof 
that  carbon  is  linked  to  carbon  in  the  alkyl  cyanides. 

II.  ISO-CYANIDES     R— N  =  C  OR  R— N=C 
ISO-NITRILES  OR  CARBYLAM1NES 

Action  of  Alkyl  Halides  and  Silver  Cyanide. — The  compounds 
formed  by  the  reaction  of  alkyl  halides  with  metal  cyanides  exhibit  a 
new  and  peculiar  case  of  somerism.  When  silver  cyanide,  instead  of 
potassium  cyanide,  acts  upon  an  alkyl  halide  there  is  formed  a  com- 
pound of  the  same  composition  as  methyl  cyanide,  viz.,  C2H3N,  but 
with  distinctly  different  properties,  i.e.,  an  isomeric  compound.  It  is 
known  therefore  as  methyl  iso-cyanide.  The  explanation  of  the  iso- 
merism  of  these  two  compounds  is  furnished  by  the  character  of  the 
products  which  they  yield  when  decomposed  with  water.  We  have 
proven  that  in  methyl  cyanide  the  methyl  carbon  atom  is  linked  to  the 
cyanogen  carbon  atom. 

CH3CN   +    2H2O         >        CH3COOH   +   NH3 

Methyl  cyanide  Acetic  acid 

In  the  products  of  this  reaction  the  two  carbons  remain  linked  together 
in  one  compound  while  the  nitrogen  breaks  away  from  the  carbon  and 
forms  ammonia. 

Nitrogen  Linked  to  Carbon. — Now  when  the  isomeric  compound, 
formed  with  silver  cyanide  and  the  methyl  halide,  is  decomposed  with 
water  the  nitrogen  of  the  cyanogen  remains  linked  to  the  methyl  carbon 
in  the  form  of  methyl  amine  and  the  other  product  contains  the  cyano- 


70  ORGANIC  CHEMISTRY 

gen  carbon  atom  which  has  broken  away  from  the  nitrogen.     The  re- 
action is 

CH3—  NC  +  2H2O        —  ->        CH3—  NH2  +  H—  COOH 

Methyl  Methyl  amine  Formic  acid 

iso-cyanide 

If  there  is  no  change  in  the  linking  of  the  other  elements  to  the 
methyl  carbon  atom  the  formation  of  methyl  amine,  in  which  we  know 
the  methyl  carbon  is  linked  to  nitrogen,  proves  that  in  the  methyl 
iso-cyanide  the  methyl  carbon  atom  is  linked  to  the  nitrogen  atom.  We 
should  compare  with  this  the  formation  of  amines  from  the  alkyl 
cyanides  by  the  action  of  nascent  hydrogen  as  given  on  the  preceding 
page. 


CH3—  CN  +  2H2        -  >        CHg—CHjy—  NH2 

Methyl  cyanide  Ethyl  amine 

In  this  case  the  reaction  proves  that  the  methyl  carbon  is  linked 
to  the  carbon  atom  of  cyanogen  and  this  carbon  becomes  a  new  chain 
carbon  so  that  the  alkyl  radical  of  the  resulting  amine  is  one  carbon 
richer  than  the  alkyl  radical  of  the  cyanide. 

Tests  for  Primary  Amines.  —  The  constitution  of  R  —  NC  for  the 
isocyanides  is  supported  also  by  their  synthesis  from  primary  amines. 
When  a  primary  amine,  R  —  NH2,  is  treated  with  chloroform  in  alkaline 
solution  an  iso-cyanide  is  formed.  Chloroform  (p.  183),  is  tri-chlor 
methane,  CHC13.  The  reaction  is, 

CH3—  N(H2)  +  C(HC13)  +  3KOH  --  >  CH3—  NC  +  3KC1  +  3H2O 

Methyl  Chloroform  Methyl 

amine  iso-cyanide 

The  two  hydrogen  atoms  of  the  primary  amine  group,  together  with  the 
one  hydrogen  atom  of  chloroform,  unite  with  the  three  chlorine  atoms  of 
chloroform  to  form  hydrochloric  acid  leaving  the  carbon  atom  of  chlo- 
roform to  take  the  place  of  the  amine  hydrogens  to  form  the  iso-cyanide. 
In  the  iso-cyanide  therefore  the  methyl  carbon  atom  must  be  linked  to  the 
•nitrogen  as  it  is  in  methyl  amine.  The  reaction  becomes  a  specific 
test  for  primary  amines  inasmuch  as  two  amine  hydrogens  are  neces- 
sary to  supplement  the  one  of  chloroform  and  form  hydrochloric  acid 
with  the  three  chlorine  atoms  present.  As  secondary  amines  have  only 
one  remaining  amine  hydrogen  atom  and  tertiary  amines  have  no 
remaining  amine  hydrogen  atom  neither  of  these  classes  of  amines  are 
able  to  form  isocyanides  with  chloroform.  The  fact  is  that  only 


ALKYL  CYANOGEN  COMPOUNDS  71 

primary  amines  do  so  react  and  the  reaction  is  a  positive  proof  that  the 
compound  is  of  this  class. 

Hofmann's  Iso-cyanide  or  Iso-nitrile  Reaction.  —  As  the  iso-cyanides 
have  a  very  characteristic  odor,  their  formation  is  easily  detected  and 
the  reaction  is  used  as  a  test  for  primary  amines. 

It  was  discovered  by  Hofmann  and  is  therefore  known  as  the  Hof- 
mann  iso  -cyanide  or  iso-nitrile  reaction.  In  this  connection  the  other 
tests  for  primary,  secondary  and  tertiary  amines  should  be  recalled 
(pp.  59-61). 

Iso-nitriles,  Carbylamines.  —  The  alkyl  cyanides  because  of  their 
relations  to  acids  are  known  as  acid  nitriles  ;  methyl  cyanide  by  hydrol- 
ysis yields  acetic  acid  and  it  is  thus  known  also  as  acetic  nitrile.  The 
iso-cyanides  being  isomeric  with  the  nitriles  are  also  termed  iso- 
nitriles.  Another  name  is  sometimes  used  because  of  their  amine 
relationship,  viz.,  carby  1  -amine  ;  methyl  iso-cyanide,  CH3  —  NC, 
being  methyl  carbylamine.  The  lower  alkyl-iso-cyanides  are  liquids 
with  a  very  strong  disagreeable  odor.  They  are  readily  hydrolized  by 
water  but  form  salts  with  hydrochloric  acid  and  also  with  silver  cyanide. 

Nitrogen  Carbon  Linkage.  —  From  their  relationship  to  primary 
amines  both  by  decomposition  and  by  synthesis  the  constitution  of  the 
isocyanides  is  proven  to  be  R  —  NC.  Taking  methyl  cyanide  and 
methyl  iso-cyanide  for  illustration  the  formulas  of  these  isomeric 
compounds  are 


N  CH3—  N^C  or  CH3—  N=C 

Methyl  cyanide  Methyl  iso-cyanide 

The  exact  nature  of  the  linkage  of  the  nitrogen  between  two  carbons  in 
the  isocyanide  has  been  explained  in  two  ways. 

The  first  and  until  recently  the  accepted  view  is  that  in  the  cyanides 
nitrogen  is  trivalent  while  in  the  iso-cyanides  it  is  pentavalent  as  shown  in 
the  above  formulas.  This  is  in  accord  with  our  assumption  that  in 
organic  compounds  carbon  is  tetravalent.  It  also  agrees  with  facts  in 
regard  to  the  element  nitrogen  for  we  know  that  nitrogen  frequently 
changes  valence  from  three  to  five. 

Bivalent  Carbon.  —  Recent  work  on  some  derivatives  of  methane 
containing  phenyl  groups,  related  to  the  hydrocarbon  benzene  to  be 
considered  in  Part  II,  have  led  to  the  view  that  carbon  is  not  always 
tetravalent  but  that  it  may  be  trivalent  or  bivalent.  If  in  the  isocyanides 
nitrogen  remains  trivalent  then  carbon  must  become  bivalent  or  else 


72  ORGANIC  CHEMISTRY 

the   four   valencies   of   the   carbon   are   not   all   satisfied,  i.e.,   it   is 
unsaturated.     Methyl  iso-cyanide  may  be  either  of  the  following: 

CH3—  N=C  CH3—  N=  C  CH3—  N--C- 

Pentavalent  N.  Trivalent  N.  Trivalent  N. 

Tetravalent  C.  Bivalent  C.  Tetra-valent 

unsaturated  C. 

Two  reactions  of  the  iso-cyanides  have  been  used  as  supporting 
either  of  the  last  two  formulas.  Methyl  isocyanide  forms  a  compound, 
CH3  —  N=C=C12,  which  in  turn  by  means  of  silver  oxide  yields  methyl 
iso-cyanate  the  constitution  of  which  is  CH3  —  N  =  C  =  O  as  we  shall 
presently  show.  These  reactions  are  analogous  to  similar  ones  which 
occur  with  carbon  monoxide,  CO,  a  compound  in  which  carbon  is 
considered  as  bivalent. 


CH3—  N=C  CH3—  N—  C—  Cl,         CH3—  N 

Methyl  iso-cyanide  Di-chloride  Methyl  iso-cyanate 

O=C  O=  C=C12  O—  C=0 

Carbon  monoxide  Carbonyl  chloride  Carbon  dioxide 

However,  as  other  recent  work  has  shown  that  oxygen  may  some- 
times be  tetravalent  as  well  as  bivalent,  the  above  relationships  between 
carbon  monoxide,  carbonyl  chloride  and  carbon  dioxide  are  possible 
of  another  explanation,  viz.,  that  the  valence  of  oxygen  changes  while  that 
of  carbon  remains  constant  as  tetravalent.  In  regard  to  the  unsaturated 
condition  of  the  carbon  by  which  two  valences  are  left  unsatisfied  we 
may  simply  say  that  such  a  condition  is  wholly  different  from  unsatu- 
ration  existing  in  compounds  containing  two  carbons  linked  together 
and  which  we  shall  study  later.  It  may  also  be  questioned  whether  the 
condition  existing  when  carbon  has  two  unsatisfied  valences  is  any 
different  from  that  which  exists  in  the  case  of  bivalent  carbon  possible 
of  changing  to  tetravalent.  The  whole  problem  of  the  exact  nature  of 
the  linkage  of  the  nitrogen  in  the  iso-cyanides  seems  to  be  one  connected 
with  the  change  in  valence  of  either  nitrogen  or  carbon.  If  the  nitrogen 
remains  constantly  trivalent  the  carbon  must  be  the  one  that  changes  to 
bivalent  while,  if  the  carbon  remains  tetravalent  the  nitrogen  must  change 
from  trivalent  to  pentavalent.  The  fact  that  the  iso-cyanides  show  no 
resemblance  to  ammonium  salts,  whereas  they  are  like  the  amines, 
indicates  that  it  is  probably  carbon  which  changes  and  that  in  this 
compound  it  is  bivalent. 


ALKVL   CYANOGEN   COMPOUNDS  73 

III.  ALKYL  ISO-CYANATES  R—  N  =  C  =  O 
THIO-CYANATES    R—  S—  C=N.    ISO  -THIO  -CYAN  AXES    R—  N  =  C  =  S 

The  isomerism  existing  in  the  case  of  cyanides  or  nitriles  and  iso- 
cyanides  or  iso-nitriles,  which  we  have  just  discussed,  is  found  also, 
in  part,  in  their  oxidation  products  the  iso-cyanates  and  in  analogous 
sulphur  compounds  the  thio-cyanates  and  iso-thio-cyanates.  We  have 
referred  to  the  fact  that  hydrocyanic  acid  like  hydrochloric  acid  yields 
an  oxygen  acid  which  though  unknown  itself  is  represented  by  well 
known  salts. 

H—  Cl  HO—  Cl  KO—  Cl 

Hydrochloric  acid  Hypochlorous  acid  Potassium  hypochlorite 

H—  CN  HO—  CN  KO—  CN 

Hydrocyanic  acid  Cyanic  acid  Potassium  cyanate 

(unknown)  (known) 

The  alkyl  derivatives  of  this  cyanic  acid,  viz.,  alkyl  cyanates,  are  not 
known  for  reactions  which  should  yield  them  do  not  do  so  though  there 
are  obtained  derivatives  of  the  polymeric  compound  cyanuric  acid 
(p.  418).  The  isomeric  alkyl  compounds  or  alkyl  iso-cyanates  are, 
however,  known.  These  compounds  may  be  made  by  the  oxidation 
of  the  corresponding  alkyl  iso-cyanides. 

CH3—  N  =  C  or  CH3—  N  =  C  -f  O    —  >    CH3—  N  =  C  =  0 

Methyl  iso-cyanide  Methyl  iso-cyanate 

The  constitution  of  the  alkyl  iso-cyanates  has  been  established  as  above 
by  the  following  facts. 

When  hydrolized  they  yield  alkyl  amines  in  which  the  alkyl  radical 
is  linked  to  nitrogen;  and  they  may  be  made,  as  previously  stated  (p.  72), 
from  the  iso-cyanides  through  the  dichloride  by  means  of  silver  oxide, 


N  =  C-fCl2        -  >  CH3—  N  =  C  =  C12 

Methyl  iso-cyanide  Di-chloride 

CH3  -  N  =  C  =  C12  +  Ag2O        —  U        CH3—  N  =  C  =  0 

Di-chloride  Methyl  iso-cyanate 

This  relationship  has  already  been  discussed  in  connection  with  its 
bearing  on  the  question  of  the  existence  of  bivalent  carbon  in  the  iso- 
cyanides. 

Thio-Compounds.  —  In  inorganic  chemistry  we  know  compounds  in 
which  oxygen  acids  and  salts  have  an  oxygen  atom  replaced  by  sul- 


74 


ORGANIC  CHEMISTRY 


phur  yielding  thio  compounds.  The  most  common  example  of  this  is 
the  case  of  thio-sulphuric  acid  and  thio-sulphates. 

HO— SO2— OH  HS— SO2— OH  NaS— SO2— ONa 

Sulphuric  acid  Thio-sulphuric  acid  Sodium  thio-sulphate 

This  same  substitution  of  sulphur  for  oxygen  occurs  in  the  case  of  cyanic 
acid  and  its  salts,  e.g.,  potassium  thio-cyanate  and  ammonium  thio- 
cyanate  used  as  reagents  in  testing  for  ferric  iron. 

HO-C^N    -  HS-C  =  N 

Cyanic  acid  Thio-cyanic  acid 

KO— C^N  KS— C^N 

Potassium  cyanate  Potassium  thio-cyanate 

NH40-C  =  N  (NH4)S-C  =  N 

Ammonium  cyanate  Ammonium  thio-cyanate 

Alkyl  Thio-cyanates ;  Alkyl  Iso-thio-cyanates. — In  the  alkyl  deriva- 
tives of  thio-cyanic  acid  we  again  have  isomerism  exactly  analogous  to 
that  in  the  unknown  cyanates  and  the  known  iso-cyanates. 

R_C=N  RO— C=N  RS— C^N 

Alkyl  cyanides  Alkyl  cyanates  Alkyl  thio-cyanates 

(unknown) 

R_N  =  CorR— N  =  C         R— N  =  C  =  0  R— N  =  C  =  S 

Alkyl  iso-cyanides  Alkyl  iso-cyanates  Alkyl  iso-thio-cyanates 

Alkyl  derivatives  of  these  cyanate  compounds  in  which  the  alkyl  radical 
is  derived  from  a  saturated  hydrocarbon  of  the  methane  series  are  not 
of  any  special  importance.  When,  however,  we  study  another  series  of 
hydrocarbons  known  -as  the  unsaturated  hydrocarbons  we  shall  find  im- 
portant derivatives  which  occur  in  nature.  We  shall  then  refer  to  this 
study  of  the  general  relationships  which  we  have  here  discussed. 


(E)    NITRO   COMPOUNDS   R— NO2 
NITROSO   COMPOUNDS   R— NO 

When  ammonia  is  oxidized  nitric  acid  is  the  result  if  the  reaction 
is  carried  to  its  limit,  but  less  complete  oxidation  produces  nitrous  acid. 

Nitro  Substitution  Products. — Nitric  acid  is  HO — NO2  and  ni- 
trous acid  is  HO — NO.  If  these  are  reduced  ammonia  is  the  result. 
When  the  silver  salt  of  nitrous  acid  acts  upon  an  alkyl  halide  a  reaction 
occurs  similar  to  that  of  potassium  cyanide  upon  the  alkyl  halides, 


NITRO    AND    NITROSO    COMPOUNDS  75 

and  a  compound  is  formed  in  which  the  halogen  of  the  halide  is  replaced 
by  the  group  NO2. 

CH3—  (I  +  Ag)N02        -  >        CH3—  N02  +  Agl 

Methyl  Silver  Nitro  methane 

iodide  nitrite 

This  group  (  —  NO2),  is  the  residue  of  nitric  acid,  HO  —  NO2,  left  when 
the  acid  hydroxyl  is  removed.  It  is  known  as  the  nitro  group,  and 
compounds  containing  it  as  nitro  compounds.  Some  of  the  higher 
paraffin  hydrocarbons  yield  nitro  compounds  when  heated  with  dilute 
nitric  acid  under  pressure  by  the  reaction 

R—  (H   +   HO)—  N02        -  >        R—  N02 

Hydrocarbon  Nitro  compound 

In  the  paraffin  series  this  reaction  and  the  products  formed  are  not  of 
especial  importance  but  we  shall  find  that  in  the  benzene  or  carbo- 
cyclic  series  the  nitro  compounds  are  easily  formed  directly  from  the 
hydrocarbons  by  action  of  nitric  acid  and  they  are  very  important 
compounds.  When  nitro  methane  is  reduced  by  nascent  hydrogen  the 
nitro  group,  (  —  NO2),  the  nitric  acid  residue,  is  reduced  to  the  ammonia 
residue,  (  —  NH2).  The  result  is  an  alkyl  amine. 

CH3—  NO2  +  3H2        -  >        CH3—  NH2  +  2H2O 

Nitro  methane  Amino  methane 

Methyl  amine 

This  is  one  of  the  general  methods  of  forming  primary  amines. 

Nitroso  Compounds.  —  When  nitrous  acid  itself,   HO  —  NO,  acts 

R\ 

upon  a  tertiary  hydrocarbon  group,  i.e.,  the  group  R-^CH  the  hydro- 

W 

gen  of  the  tertiary  carbon  group  is  removed  together  with  hydroxyl 
of  the  nitrous  acid,  and  a  compound  is  formed  containing  the  nitrous 
acid  residue  (  —  NO)  known  as  the  nitroso  group.  These  compounds 
are  analogous  to  nitro  methane,  but  contain  one  oxygen  less. 

R  R\ 

HO)NO  —  >        RC—  NO  +  H2O 


Tertiary  Nitroso 

hydrocarbon  compound 


A  similar  reaction  takes  place  also  as  we  have  recently  discussed  (p. 
61)  with  the  secondary  amine  group,  the  product  in  this  case  being 


76  OEGANIC  CHEMISTRY 

known  as  a  nitroso  amine.  In  both  cases  the  reaction  is  with  the  one 
remaining  hydrogen  linked  to  carbon  or  nitrogen. 

R  R, 

/>N(H  +  HO)NO        >  ^>N— NO 

R/  R/ 

Secondary  Nitroso 

amine  amine 

Nitroso  compounds,  like  the  nitro  compounds,  are  converted  into 
amines  by  reduction  with  hydrogen. 

(F)  METALLIC    ALKYL    COMPOUNDS— OR  GANG-METALLIC 

COMPOUNDS 

I.  ZINC  ALKYLS    Zn— R2   ALKYL  ZINC  HALIDES   R— Zn— I 

Still  one  more  class  of  alkyl  derivatives  should  be  mentioned  in 
this  part  of  our  study.  These  are  compounds  of  the  alkyl  radicals  with 
metals,  and  are  known  in  general  as  organo-metallic  compounds.  A 
large  number  of  metals  form  compounds  of  this  kind,  and  the  ease  of 
formation  seems  to  have  a  definite  relation  to  the  position  of  the  metal 
in  the  periodic  system.  Compounds  of  the  alkali  metals  with  organic 
radicals  have  not  been  isolated,  but  they  probably  exist  as  intermedi- 
ate products  and  also  as  double  compounds  with  other  metallic  alkyl 
compounds.  The  two  groups  of  these  compounds  which  we  shall 
briefly  consider  are  those  of  zinc  and  magnesium. 

When  zinc  acts  upon  alkyl  iodides  in  the  Frankland  reaction  (p. 
1 6),  the  final  product,  is  a  hydrocarbon  composed  of  two  of  the  alkyl 
radicals  linked  together. 

CH3— (I  +  Zn  +  I)— CH3        >        CH3— CH3  +  ZnI2 

Methyl  Ethane 

iodide 

Two  intermediate  products  of  this  reaction  can  be  isolated,  and  they 
have  been  shown  to  have  the  composition  CH3 — Zn — I,  methyl  zinc 
odide  and  Zn(CH3)2,  zinc  methyl.  The  reactions  are: 

2CH3— I  +  2Zn        >         2CH3— Zn— I 

Methyl  Methyl  zinc 

iodide  iodide 

2CH3— Zn— I        >        Zn(CH3)2  +  ZnI2 

Methyl  zinc  iodide  Zinc  methyl 

The  zinc  methyl  then  reacts  with  methyl  iodide  as  follows: 

Zn(CH3)2  +  2CH3I        >         2CH3— CH3  +  ZnI2 

Zinc  methyl  Ethane 


2CH3—  I  +  2Zn    > 

Methyl 
iodide 

2CH3—  Zn—  I 

Methyl  zinc 
iodide 

ZnI2      + 

Zn(CHa 

Zinc 
methyl 

1)2  +  (2H20) 

2CH3—  I  +  2Zn 

Methyl 
iodide 

> 

2CH3—  Zn—  I 

Methyl  zinc 
iodide 

ZnI2  -f- 

Zn(CH 

Zinc 
methyl 

3)2  +  (2CH3—  r 

METALLIC  ALKYL  COMPOUNDS  77 

Also  the  zinc  methyl  may  react  with  water  when  a  lower  hydrocarbon 
is  formed,  viz.,  the  one  corresponding  to  the  alkyl  radical,  in  this 
case  methane. 

Zn(CH3)2  +  2H2O        -  >         2CH4  +  Zn(OH)2 

Zinc  methyl  Methane 

Writing  out  these  reactions  together  in  order  to  make  it  clear  we  nave: 


2CH4     +   Zn(OH) 

Methane 


->  2CH3— CH3  +  ZnI2 

Ethane 

Frankland  Reaction  or  Synthesis. — The  discovery  of  the  zinc 
alkyls  was  made  by  Frankland  in  1850  and  the  reactions  and  syntheses 
above  are  known  as  the  Frankland  Reaction. 

H.  ALKYL  MAGNESIUM  HALIDES   R— Mg— I 

Grignard  Reaction. — The  magnesium  alkyl  compounds  had  been 
known  but  not  used  in  synthetic  reactions  until  1899  when  Barbier 
and  in  1900  Grignard  used  them  in  this  way.  Since  then  the  applica- 
tions of  the  general  reaction  have  been  very  numerous.  It  is  known  as 
the  Grignard  Reaction  and  may  be  illustrated  as  follows: 

2C2H5— I  +  2Mg        >        2C2H5— Mg— I1 

Ethyl  Ethyl  magnesium  iodide 

iodide  Grignard  reagent 

With  water  the  ethyl  magnesium  iodide  yields  the  hydrocarbon  cor- 
responding to  the  alkyl  radical  just  as  in  the  Frankland  reaction,  as 
follows: 

2C2H5— Mg— I  +  2H2O >     2C2H6  +  MgI2  +  Mg(OH)2 

Ethyl  magnesium  Ethane 

iodide 

1  This  compound  is  prepared  in  an  ether  solution,  and  it  is  believed  that  the  ether 
enters  into  the  product  and  that  the  formula  is  probably  not  the  simple  magnesium 
alkyl  halide,  but  is 

C2H5V        /Mg— C2H£ 

CaH6 


78  ORGANIC  CHEMISTRY 

With  compounds  containing  the  carbonyl  group  (  =  CO),  such  as  alde- 
hydes, ketones  or  acid  chlorides  the  alkyl  magnesium  halides  react  as 

follows: 

O(MgI 

CH3— C  =  0  +  CH3— Mg— I  -  rr*  CH3— C— CH3  +  HO)— H > 

CH3  CH3 

Acetone 

OH 

CH3— C— CH3  +  Mg  (OH)  I 
CH3 

Tertiary  butyl 
alcohol 

These  general  reactions  of  the  organo-metallic  compounds  in  the 
Frankland  reaction  and  the  Grignard  reaction,  especially  the  latter,  are 
applicable  with  modifications  in  a  great  variety  of  cases,  so  that  by  means 
of  them  alkyl  radicals  may  be  introduced  into  various  desired  positions. 
A  further  discussion  of  these  reactions,  at  this  time,  is  not  necessary 
or  desirable  in  this  work,  but  they  will  be  referred  to  in  connection 
with  certain  compounds  where  they  are  especially  important. 


(G)  MONO-HYDROXYL  SUBSTITUTION  PRODUCTS- 
ALCOHOLS 

GENERAL 

We  come  now  to  a  series  of  compounds  which  has  in  it  many  well- 
known  substances,  and  to  which  the  class  name  of  alcohols  has  been  given. 
The  two  most  common  representatives  of  the  series  are  ordinary  alco- 
hol or  grain  alcohol  and  wood  alcohol.  Both  are  valuable  commercial 
substances,  the  former  being  obtained  by  the  distillation  of  fermented 
grain  or  fruit,  the  latter  by  the  distillation  of  wood,  hence  their  names. 
The  composition  and  empirical  formulas  of  the  two  are  similar,  viz., 

Alcohol,  C2H6O  Wood  alcohol,  CH4O 

Taking  ordinary  alcohol  as  typical  of  the  entire  series  we  may  ask,  how 
is  it  synthesized,  how  does  it  react  with  other  substances,  and  what  do 
these  reactions  show  as  to  its  constitution? 


ALCOHOLS  79 

Alcohol  not  an  Oxide. — In  the  first  place  the  composition  of  alco- 
hol, C2H6O,  is  striking,  in  that  it  consists  of  carbon  and  hydrogen  in 
exactly  the  same  ratio  as  in  ethane,  and  in  addition  to  this  one  atom  of 
oxygen.  This  would  seem  to  indicate  that  alcohol  is  a  simple  oxide 
of  the  hydrocarbon  ethane,  i.e.,  (C2He)O.  Can  we  say,  however,  that 
ethane,  or  the  ethane  grouping  itself  is  present  in  the  molecule  of  al- 
cohol, i.e.,  are  the  six  hydrogen  atoms  in  alcohol  in  the  same  relation  to 
the  carbon  as  they  are  in  ethane?  Or,  on  the  other  hand,  can  we  show 
positive  proof  that  some  other  constitution  is  supported  by  facts? 
Several  reactions  do  give  this  latter  proof. 

Reaction  of  Alcohol  and  Sodium. — When  metallic  sodium  acts  on 
alcohol,  hydrogen  gas  is  set  free  and  a  new  compound  known  as  sodium 
alcoholate  is  formed.  The  amount  of  hydrogen  evolved  is  in  the  ratio 
of  1.008  parts  by  weight  of  hydrogen  to  23.0  parts  of  sodium.  That  is, 
one  atom  of  hydrogen  is  set  free,  and  one  atom  of  sodium  takes  its  place 
in  the  alcohol  molecule.  The  composition  of  the  new  compound  is 
C2H5NaO.  The  important  fact  for  our  present  consideration  is  that 
only  one  hydrogen  is  ever  thus  removed  by  sodium.  Our  proof  that  the 
six  atoms  of  hydrogen  in  ethane  are  all  alike  in  their  relation  to  carbon 
is  in  the  fact  that  one,  two,  three,  four,  five  or  six  of  them  are  possible 
of  substitution  by  chlorine.  Also  when  only  one  hydrogen  is  thus  sub- 
stituted by  chlorine  it  makes  no  difference  which  one  of  the  six  is  re- 
placed for  only  one  mono-chlor  ethane,  C2H5C1,  is  known  (p.  n). 
In  alcohol  it  has  never  been  possible  to  remove  more  than  one  hydrogen 
by  means  of  sodium.  Plainly,  then,  one  of  the  six  hydrogen  atoms  in 
alcohol  is  different  from  the  other  five.  This  might  be  indicated  by  writing 
the  formula  C2H&HO,  and  the  reaction 

C2H5HO  +  Na        >        C2H6NaO  +  H 

Alcohol  Sodium 

alcoholate 

Now  this  reaction  of  alcohol  and  sodium  is  strikingly  similar  to  the 
reaction  of  water  and  sodium.  We  write  this  latter  reaction : 

H— O— H  +  Na  — >        Na^-OH  -f  H 

Water  Sodium 

hydroxide 

Water  is  considered  as  a  combination  of  hydrogen  and  the  group 
( — OH).  There  is,  however,  probably  no  difference  in  the  hydrogen 
atoms,  either  one  of  them  being  removable,  the  other  remaining  in 


80  ORGANIC  CHEMISTRY 

combination  with  oxygen  as  OH.  That  is,  water  is  H — O — H.  If  then 
the  similarity  of  the  reaction  of  alcohol  and  water  indicates  that  the 
two  compounds  are  similar  in  constitution  the  hydrogen  atom  of  alco- 
hol which  is  replaceable  by  sodium  is  linked  to  the  oxygen  rather  than 
to  the  carbon.  We  may  express  this  in  our  formula  by 

H    H 

C2H5— O— H        or        H— C— C— OH  Alcohol 

I       I 
H    H 

Reaction  of  Alcohol  and  Phosphorus  Tri-chloride. — Three  other 
reactions  also  prove  that  in  alcohol  we  have  the  oxygen  and  hydro- 
gen in  the  same  grouping  as  in  water,  i.e.,  as  ( — O — H).  Two  of  these 
reactions  are  with  the  chlorides,  or  other  halogen  compounds  of  phos- 
phorus. Using  the  chlorides  for  illustration  there  are  two  chlorides 
of  phosphorus,  viz.,  PC13,  phosphorus  tri-chloride  and  PQ5,  phos- 
phorus penta-chloride.  The  first  one,  phosphorus  tri-chloride,  reacts 
with  water  as  follows: 

3H20  +        PC13       -»    3HC1      +      H3P03 

or 

3H— O— H        +        PC13       — >    3HC1      +      P(OH)3 

Water  Phosphorus  Hydrogen  Phosphorous 

tri-chloride  chloride  acid 

The  chlorine  of  the  phosphorus  tri-chloride  takes  the  place  of  the  hy- 
droxyl group  of  water,  or,  in  other  words,  the  phosphorus  removes  the 
hydroxyl  and  unites  with  it  forming  an  hydroxyl  compound,  i.e., 
P(OH)3  or  H3PO3,  phosphorous  acid.  When  phosphorus  tri-chloride 
reacts  with  alcohol  the  products  of  the  reaction  are  found  to  be  ethyl 
chloride  and  phosphorous  acid,  and  we  may  write  the  reaction: 

3C2H60  +        PC13  ->        3G2H5— Cl      +      H3P03 

3C2H5— OH        +        PC13  -*        3C2H5— Cl      +      P(OH)3 

Alcohol  Ethyl  chloride  Phosphorous 

acid 

The  two  reactions  then  of  phosphorus  tri-chloride  with  water  and  with 
alcohol  are  exactly  analogous.  Phosphorous  acid  is  formed  in  both 
cases  due  to  the  union  of  phosphorus  with  the  (OH)  group.  In  the 
case  of  water  a  compound  of  hydrogen  and  chlorine  is  the  other  product, 


ALCOHOLS  8 1 

while  with  alcohol  it  is  a  compound  of  the  radical  ethyl  and  chlorine. 
If  then  we  are  correct  in  considering  water  as  hydrogen  linked  to  hy- 
droxyl,  i.e.,  H — OH  alcohol  must  be  ethyl  linked  to  hydroxyl,  i.e., 
C2H5 — OH.  The  hydrogen  in  the  water  becomes  the  radical  ethyl  in 
alcohol,  and  the  hydroxyl  group  is  common  to  both. 

When  the  other  chloride  of  phosphorus,  phosphorus  penta-chloride 
PCls  reacts  with  water  a  reaction  takes  place,  in  which  it  is  probable 
that  two  chlorine  atoms  from  the  penta-chloride  exchange  places  with 
the  oxygen  of  the  water,  two  molecules  of  hydrochloric  acid  being  thus 
formed. 

H— O— H        +        PC15          — >        H— Cl     Cl— H      +      POC13 

Water  Phosphorus  Phosphorus 

penta-chloride  oxy -chloride 

Now  with  ethyl  alcohol  an  exactly  analogous  reaction  occurs  and  the 
products  are  phosphorus  oxy-chloride,  hydrochloric  acid  and  the 
chloride  of  the  alkyl  radical  ethyl.  It  must  be,  therefore,  that  the  radical 
ethyl  in  alcohol  occupies  the  place  of  one  of  the  hydrogen  atoms  in 
water,  the  other  hydrogen  remaining  as  part  of  the  hydroxyl  group. 
The  reaction  is  then, 

C2H5— O— H  +  PC15 >        C2H5— Cl     Cl— H  +  POC13 

Alcohol  Ethyl 

chloride 

These  two  reactions  of  the  chlorides  (or  other  halogen  compounds)  of 
phosphorus  are  characteristic  of  all  compounds  containing  the  hy- 
droxyl group,  and  are  used  as  proof  of  the  presence  of  this  group. 

Reaction  of  Alcohol  and  Hydrobromic  Acid. — The  third  reaction 
which  proves  the  presence  of  the  hydroxyl  group  in  alcohol  is  with  the 
halogen  binary  acids.  When  hydrochloric,  or  better  hydrobromic  or 
hydriodic  acid,  acts  upon  hot  alochol  a  partial  decomposition  of  the 
alcohol  takes  place  and  the  ethyl  halide  and  water  are  formed 

C2H5— (OH  +  H)— Br  ~~-  C2H5— (Br  +  H)— OH 

Alcohol  Ethyl  bromide 

This  reaction  proves  even  more  conclusively  that  water  and  alcohol 
are  analogous  compounds  for  in  it  the  water  is  formed  by  exchanging 
the  ethyl  radical  for  hydrogen. 

Synthesis  of  Alcohol  from  Alkyl  Halides. — This  is  shown  also  in 
the  converse  way  by  the  fact  that  in  the  reaction  as  given  only  a  portion 
of  the  alcohol  is  converted  into  ethyl  bromide  because  when  a  certain 


82  ORGANIC  CHEMISTRY 

amount  of  water  has  been  formed  the  reaction  reverses  and  the  water 
reacts  upon  the  ethyl  bromide  reforming  alcohol  and  hydrobromic  acid. 
The  reaction  is  therefore  written  with  the  double  arrow  which  indicates 
Us  reversible  character.  If,  in  the  reverse  reaction,  some  alkali,  NaOH, 
is  added  with  the  water  then  the  hydrobromic  acid  formed  is  neutral- 
ized to  sodium  bromide  and  the  reaction  therefore  proceeds  in  one 
direction  until  all  of  the  ethyl  bromide  is  decomposed  and  converted 
into  alcohol.  This  gives  us  a  general  method  of  synthesizing  alcohols 
from  alky  I  halides. 
R_(X  +  H)— OH  (+NaOH)  >  R— OH  +  NaX  +  H2O 

Alkyl  An 

halide  alcohol 

The  general  discussion  of  such  a  reversible  reaction  and  the  methods  of 
controlling  it  will  be  given  later  when  we  study  the  esters,  (p.  140). 
This  synthesis  of  alcohols  from  alkyl  halides  takes  place  much  better 
if  instead  of  water  we  use  another  hydroxide,  viz.,  silver  hydroxide, 
AgOH,  (moist  silver  oxide,  Ag2O  +  H2O)  which  forms  an  insoluble 
silver  salt  with  the  halogen,  the  reaction  thus  proceeding  in  only  one 
direction. 

C2Ho— (I  +  Ag)— OH         — >        C2H6— OH  +  Agl 

Ethyl  iodide  Silver  Alcohol 

hydroxide 

The  group  ( — O — H)  whether  in  water,  H — OH,  sodium  hydroxide, 
Na — OH,  silver  hydroxide,  Ag — OH,  or  phosphorous  acid,  P  =  (OH)3, 
is  a  mono-valent  grotip.  This  is  because  bivalent  oxygen  has  only  one 
valence  satisfied  by  hydrogen,  the  other  one  remaining  free,  giving  the 
group  a  valence  of  one.  This  group  or  radical  which  forms  inorganic 
compounds  known  as  hydroxides  is  known  in  organic  chemistry  as 
hydroxy\. 

Alcohol  of  Crystallization. — One  more  reaction  or  property  of  alco- 
hol which  shows  its  similarity  to  water  and  which  might,  indeed,  be 
much  more  conclusive  if  we  understood  more  thoroughly  the  way  water 
itself  acts,  is  that  alcohol  like  water  forms  crystalline  compounds  with 
certain  anhydrous  substances.  In  case  of  water  we  term  it  water 
of  crystallization,  so  we  may  call  its  analogue  alcohol  of  crystallization. 
Calcium  chloride,  CaCl2,  forms  crystals  containing  alcohol  of  crystal- 
lization. 

Water  Type  Compounds. — Alcohol  is  thus  a  compound  of  the  same 
general  character  as  water,  or  as  we  may  say,  it  "belongs  to  the  water 


ALCOHOLS 


83 


type.  It  is  related  to  water  in  that  the  hydrogen  is  replaced  by  an  or 
ganic  radical.  We  may  look  upon  the  following  four  compounds  as 
belonging  to  this  type, 

Water  (hydrogen  hydroxide)  H  —  OH 

Bases  or  alkalies  (metal  hydroxides)  Na  —  QH       or    M  —  OH 

Acids  (oxygen  acids)  (non-metal  hydroxides)  P  —  (OH)3orNM  —  OH 
Alcohols  (alkyl  hydroxides)  C2H5—  OH       or    R—  OH 

We  shall  find  later  that  there  are  other  groups  of  organic  hydroxyl 
compounds  known  which  are  not  alcohols.  They  are  not,  however, 
simple  alkyl  hydroxides. 

Hydroxyl  Substitution  Products.  —  All  of  the  preceding  facts  lead 
to  the  conclusion  that  alcohol  is  a  compound  in  which  the  ethyl  radical 
is  linked  to  the  hydroxyl  radical,  i.e.,  it  is  the  hydroxyl  substitution  prod- 
uct of  ethane  or  hydroxy  ethane.  Alcohols  thus  belong  to  the  same 
general  class  of  compounds  as  the  halogen  substitution  products.  The 
relationship  between  the  hydrocarbons,  the  halogen  substitution  prod- 
ucts, alkyl  halides  and  the  hydroxyl  substitution  products,^  alcohols, 
may  be  shown  as  follows: 

H    H 


Ethane 


C2HB—  H;       CH3—  CH2—  H,       H—  C—  C—  H 


H    H 
H    H 


Ethyl  chloride     C2H5—  Cl,       CH3—  CH2—  Cl       H—  C—  C—  Cl 

I      I 
H    H 

H    H 


Ethyl  alcohol      C2H5—  OH,    CH3—  CH2—  OH,    H—  C—  C—  OH 

H    H 

The  general  formulas  of  these  three  groups  of  compounds  being 


(CnH2B  +  o—ir  ' 

Hydrocarbons 


—  x 

Alkyl  halides 


(CJWO-OH 

Alcohols 


84  ORGANIC  CHEMISTRY 

Methyl  Alcohol. — The  alcohol  which  we  have  used  as  an  illustration 
of  the  group  is  the  ordinary  grain  alcohol  or  ethyl  alcohol,  C2H5 — OH. 
The  other  common  alcohol  is  the  one  known  as  wood  alcohol  or  methyl 
alcohol  which,  by  reactions  exactly  similar  to  those  we  have  been  dis- 
cussing, has  been  proven  to  bear  the  same  relation  to  methane  that 
ethyl  alcohol  does  to  ethane. 

Methyl  alcohol,    Wood  alcohol,    Hydroxy  methane,     CH3 — OH 
Ethyl  alcohol,       Alcohol,  Hydroxy  ethane,        C2Hb — OH 

Homologous  Series  of  Alcohols. — As  hydroxyl  substitution  products 
of  the  hydrocarbons  the  alcohols  form  an  homologous  series  analogous 
to  that  of  the  alkyl  halides  or  halogen  substitution  products.  Methyl 
and  ethyl  alcohol  are  thus  the  first  two  members  of  such  a  series  de- 
rived from  the  methane  or  paraffin  hydrocarbons. 

Names  of  Alcohols. — According  to  the  old  system  of  nomenclature 
the  alcohols  were  not  named  as  hydroxyl  substitution  products,  e.g., 
ethyl  hydroxide,  thus  making  the  names  analogous  to  those  of  the  alkyl 
halides.  Instead  of  this  the  class  name,  alcohol,  was  used  together 
with  the  name  of  the  alkyl  radical  present.  In  some  of  the  higher  mem- 
bers of  the  series  the  numerical  name  for  the  radical  was  replaced  by 
a  name  derived  usually  from  the  natural  source  of  the  alcohol.  Thus 
amyl,  cetyl,  ceryl  and  myricyl  alcohols  for  the  five,  sixteen,  eighteen  and 
thirty  carbon  compounds  respectively.  According  to  the  official  no- 
menclature the  hydrocarbon  name  is  simply  changed  by  dropping  the 
final  e  and  adding  the  termination  ol,  indicating  alcohol,  thus,  methan- 
ol,  ethan-ol,  pentan-ol,  hexan-ol,  etc. 

The  more  important  normal,  primary  alcohols  of  the  series,  with 
some  of  their  physical  constants  are  given  in  Table  IX  and  in  Table  X 
are  given  the  isomeric  alcohols  related  to  propane  butane  and  pentane 
with  the  number  of  known  and  possible  isomers  of  a  few  of  the  higher 
members. 

Isomerism  of  the  Alcohols. — As  they  are  hydroxyl  substitution 
products  the  isomerism  of  the  alcohols  is  like  that  of  the  halogen  sub- 
stitution products,  alkyl  halides.  This  will  -be  seen  by  examination 
of  Table  X.  They  possess  the  normal  and  iso  together  with  the  pri- 
mary, secondary  and  tertiary  characters  (pp.  27, 49).  We  have  spoken  of 
isomerism  of  this  kind  as  it  occurs  also  in  the  isomeric  hydrocarbons  as 
structural  isomerism.  In  the  case  of  the  hydrocarbons  this  isomerism  is 


ALCOHOLS  85 

TABLE  IX. — NORMAL  PRIMARY  ALCOHOLS  OF  THE  SATURATED  SERIES 


Common  name 

Official  name 

Formula 

M.P. 

B.P. 

Sp.  Gr. 

Methyl  alcohol 

Methanol. 

CHs—  OH 

at  760  m.m. 
64  s° 

ato° 
o  812 

Ethyl  alcohol  

Ethanol  

C2H6—  OH 

-130° 

78° 

o  806 

Propyl  alcohol  

Propanol  

C3H7—  OH 

07° 

0.817 

Butyl  alcohol 

Butanol 

C4H9—  OH 

117° 

o  82^ 

Pentyl  or  amyl  al- 
cohol   

Pentanol  

C6Hn—  OH 

138° 

o  820 

Hexyl  alcohol  
Heptyl  alcohol  
Octyl  alcohol  

Hexanol  
Heptanol  
Octanol  

CeHia—  OH 
C7H16—  OH 
CfjHn—  OH 

157° 
176° 
I9<5° 

0.833 
0.836 

o  830 

Nonyl  alcohol  
Decyl  alcohol         .  . 

Nonanol  
Decanol  

C9H19—  OH 

-     5° 

+     7° 

-213° 

2SI° 

0.842 

at  M.P. 

o  8^0 

Dodecyl  alcohol  
Tetradecyl  alcohol  .  . 
Hexadecyl  or  cetyl 
alcohol  

Dodecanol  
Tetradecanol  . 

Hexadecanol 

C12H25-OH 
C14H29—  OH 

C16H33—  OH 

24° 

38° 
50° 

at  15  m.m. 

143° 
167° 

100° 

0.831 
0.824 

0.818 

Octadecyl  alcohol.  .  . 
Ceryl  alcohol 

Octadecanol.  . 
Heptacosanol 

C18H37—OH 
C27H65—  OH 

59° 
76° 

211° 

0.813 

Myricyl  alcohol  

Triacontanol.  . 

CsoHei—  OH 

86° 

0.808 

due  entirely  to  a  difference  in  the  chain  of  carbons  present  in  the  com- 
pound. In  the  case  of  the  halogen  and  hydroxyl  substitution  products 
the  hydrocarbon  chain  may  remain  the  same,  and  isomerism  may  be 
due  to  the  different  position  in  which  the  halogen  or  hydroxyl  enters  the 
chain.  To  illustrate  with  four  of  the  isomeric  pentanols. 

Pentanol-i,     CH3— CH2— CH2— CH2— CH2OH 

Pentanol-2,  CH3— CH2— CH2— CH(OH)— CH3 

2-Methyl  butanol-4,     CH3— CH— CH2— CH2OH 

I 
CH3 

2-Methyl  butanol-3,     CH3— CH— CH(OH)— CH3 


CH3 


86 


ORGANIC  CHEMISTRY 


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ALCOHOLS  87 

The  above  formulas  represent  different  isomers  because  the  chain 
hydrocarbon  is 'normal  or  straight  in  two  cases,  and  iso  or  branched  in 
the  others,  as  shown  in  the  vertical  pairs  of  formulas.  On  the  other 
hand  difference  in  structure  results  because  the  hydroxyl  is  substituted 
in  a  different  carbon  group,  as  shown  in  the  horizontal  pairs  of  formulas. 

Now  the  first  kind  of  structural  isomerism  is  called  root  isomerism 
or  chain  isomerism  and  is  the  only  kind  present  in  the  case  of  hydrocar- 
bons. The  second  is  known  as  position  isomerism  and  is  possible  in 
all  substitution  products  of  the  hydrocarbons.  Both  are,  however, 
included  in  the  term  structural  isomerism. 

Names  of  Isomeric  Alcohols. — The  naming  of  isomeric  alcohols 
follows  the  same  plan  as  that  of  the  isomeric  alkyl  halides.  In  the 
latter,  however,  the  halogen  as  well  as  the  substituting  alkyl  radical 
is  considered  as  a  substituting  group  in  the  chain  of  carbons  which 
gives  the  name  to  the  compound,  viz.,  the  longest  straight  chain  of 
carbon  atoms  present.  In  the  alcohols  the  hydroxyl  group  is  considered 
a  part  of  the  chain  name,  which,  therefore,  takes  the  alcohol  termination. 
The  position  of  the  hydroxyl  is  designated  by  a  number  as  in  other 
cases.  This  will  be  clear  from  the  following  examples  in  which  hy- 
droxyl and  chlorine  are  substituted  in  the  same  hydrocarbon  and  in 
the  same  position. 

CH3— CH— CHC1— CH3  2-Methyl  3-chlor  butane 

I 
CH8 

CH3— CH— CH(OH)— CH3          2-Methyl  butan-ol-3 

I 
CH3 

The  names  of  the  isomeric  alcohols  in  Table  X  will  thus  be  clearly  under- 
stood. The  position  isomerism  gives  rise  to  the  primary,  secondary 
and  tertiary  alcohols  characterized  by  the  groups, 

R  R 

I  I 

R— CH2— OH  R— CH— OH  R— C— OH 

Primary  alcohols  Secondary  alcohols 

R 

Tertiary  alcohols 

This  is  exactly  analogous  to  primary,  secondary  and  tertiary  alkyl 
halides  as  discussed  under  those  compounds  (p.  47). 


88  ORGANIC  CHEMISTRY 

Stereo  Isomerism 

Optical  Activity. — We  come  now,  in  the  case  of  th'e  isomeric  alco- 
hols, to  a  new  and  most  interesting  example  of  isomerism.  The  five 
carbon  alcohol  2-methyl  butanol-i,  differs  from  the  other  seven  struc- 
turally isomeric  amyl  alcohols  not  only  in  structure,  but  also  in  other 
striking  ways.  Three  different  amyl  alcohols  are  known  all  of  which 
have  the  constitution  of  2-methyl  butanol-i.  Two  of  these  three  are 
known  as  optically  active,  all  the  other  amyl  alcohols  being  inactive. 
Certain  substances  either  in  the  crystalline  form,  as  in  the  case  of 
quartz;  in  solution,  as  in  the  case  of  sugar;  or  in  the  liquid  form, 
as  in  the  case  of  the  alcohol  we  are  considering;  possess  this  phys- 
ical property  of  optical  activity.  This  property  is  shown  by  the  fact 
that  the  compound  has  the  power  to  turn  or  rotate  the  plane  of  vibra- 
tion of  a  ray  of  light  that  has  been  polarized. 

Dextro,  Levo  and  Inactive  Compounds. — All  optically  active  sub- 
stances rotate  the  plane  of  polarized  light  either  in  one  direction  to  the 
right  or  in  the  contrary  direction  to  the  left.  On  this  account  they  are 
known  as  right-handed  or  dextro-rotatory  and  left-handed  or  lew-rotatory. 
The  phenomenon  of  polarization  being  purely  a  physical  one  will  not 
be  discussed  here.  An  explanation  of  it  may  be  found  in  text  books 
of  physics  or  in  chemical  books  which  consider  in  detail  such  subjects 
as  the  sugars.  All  that  need  be  added  is  that  optically  active  com- 
pounds are  readily  examined  by  means  of  an  instrument  known  as  a 
polariscope  and  the  direction  of  rotation  (right  or  left)  and  the  exact 
amount  of  rotation  in  degrees  may  be  accurately  determined. 

What  we  are  concerned  with  at  this  time  is  an  explanation  on 
chemical  grounds  of  the  important  fact  that  three  amyl  alcohols,  or 
pentanols,  are  known  all  of  which  possess  the  same  structural  formula, 
viz.,  2-methyl  butanol-i ;  and  that  one  of  these  compounds  is  dextro- 
rotatory, another  is  lew-rotatory  and  the  third  one  is  inactive.  These 
three  are  different  individual  compounds  with  practically  the  same 
physical  properties  other  than  optical.  The  inactive  variety  of  2- 
methyl  butanol-i  differs,  however,  from  the  other  seven  structurally 
isomeric  pentanols  which  are  likewise  inactive  not  only  in  its  structure 
but  also  in  the  fact  that  by  means  of  certain  reactions  there  may  be 
obtained  from  it  both  the  dextro-rotatory  and  the  levo-rotatory  com- 
pounds. In  it,  and  in  other  inactive  compounds  of  the  same  kind, 
there  are  present  equivalent  amounts  of  the  two  oppositely  active  compounds, 


ALCOHOLS  89 

the  inactivity  being  due  to  a  balancing  of  one  activity  by  the  other.  When 
the  two  active  compounds  are  obtained,  as  above,  from  the  inactive 
one  we  say  that  the  inactive  compound  has  been  split  into  its  two 
optical  components.  The  other  seven  inactive  amyl  alcohols  have 
never  been  thus  split  into  optical  components. 

Pasteur. — The  discovery  that  optically  active  substances  exist  in 
two  forms  dextro-rotatory,  and  lew-rotatory  and  that  the  corresponding 
inactive  compound  is  composed  of  equal  amounts  of  the  dextro  and  levo 
and  may  be  split  into  these  two  forms,  was  made  by  Pasteur,  who, 
because  of  his  later  remarkable  work  in  the  field  of  pathology,  is  not 
generally  known  as  a  chemist.  Pasteur  made  this  discovery  during  a 
study  of  tartaric  acid,  and  it  will  be  spoken  of  again  when  we  come  to 
that  compound. 

Though  we  can  thus  explain  the  existence  of  these  three  alcohols 
which  possess  the  structural  formula  of  2-methyl  butanol-i  we  do  it  in 
each  case  only  in  terms  of  the  other  two,  i.e.,  the  inactive  compound 
consists  of  a  mixture  of  the  dextro  and  levo  forms  and  conversely. 
How  then  can  we  account  for  the  fact  that  the  two  active  isomers  and, 
therefore,  the  three  together  are  possible  with  the  same  structural 
formula? 

Theory  of  van't  Hoff-LeBel. — Two  men  independently  of  each  other 
advanced  a  theory  which  explains  these  facts.  One,  a  Dutch  chemist 
by  the  name  of  van't  Hoff,  and  the  other  a  French  chemist,  LeBel. 
On  examining  the  structural  formulas  of  optically  active  compounds 
these  men  each  saw  that  they  differed  in  a  common  way  from  all  opti- 
cally inactive  compounds  which  were  not  possible  of  being  split  into 
optical  components.  Taking  as  an  illustration  the  alcohol  with  which 
we  are  dealing,  viz.,  active  amyl  alcohol  or  2-methyl  butanol-i  we  see 
by  examining  its  formula  that  one  of  the  carbon  atoms  is  characteris- 
tically different  from  all  of  the  others. 

(H) 

(CH3— CH2)— C— (CH2OH)     2-Methyl  butanol-i 

(CHg) 

Carbon  atom  2  has  linked  to  it  a  methyl  group  ( — CH3),  a  hydrogen 
atom  ( — H),a  primary  alcohol  group  ( — CH2OH),  and  an  ethyl  group 
(CH3 — CH2 — ),  i.e.,  there  are  four  different  groups  or  atoms  linked  to 


QO  ORGANIC  CHEMISTRY 

this  one  carbon.  It  is  the  only  carbon  in  the  molecule  having  such 
relations. 

Asymmetric  Carbon, — Now  van't  Hoff  and  LeBel  found  that  all 
optically  active  compounds  contained  at  least  one  such  carbon  atom.  They 
ascribed  the  existence  of  two  optically  active  forms  to  the  presence  in 
the  compound  of  this  unsymmetrically  related  or  asymmetric  carbon 
atom.  The  asymmetry  of  the  compounds,  in  that  one  form  is  dextro- 
rotatory the  other  levo-rotatory,  is  due  to  this  asymmetric  arrangement 
of  the  molecule  in  space.  We  emphasized  the  fact  that  our  structural 
formulas  as  we  have  been  using  them  are  simply  plane  representations 
of  relationships,  and  indicate  nothing  as  to  the  arrangement  in  space  of 
the  atoms  or  groups  in  a  molecule.  The  theory  of  van't  Hoff  and  LeBel 
considers  the  molecule  as  it  is  arranged  in  space.  The  isomerism  so 
explained  is  known  as  stereo-isomerism  or  space  isomerism. 

Stero-isomerism. — According  to  LeBel  the  simple  fact  that  a  mole- 
cule is  built  up  asymmetrically  in  space  will  explain  all  cases  of  opti- 
cally active  compounds  existing  in  the  three  forms  mentioned.  An 
arrangement  unsymmetrical  on  one  side  would  explain  a  dextro  form 
and  the  arrangement  unsymmetrical  on  the  other  would  explain  the 
levo  form,  a  mixture  of  an  equal  number  of  molecules  of  the  two  forms 
being  inactive.  He  assumed  no  definite  arrangement  for  the  space  re- 
lations of  the  atoms  or  groups,  van't  Hoff,  however,  with  the  same 
idea,  went  a  step  further  and  devised  a  definite  geometrical  arrange- 
ment of  the  atoms  in  space  which  would  explain  the  asymmetry  and 
thus  the  three  isomeric  compounds. 


- 


Methane  Methyt-a  butono\-i 

CHj-CH^-CH-CI^OH 
P.O.  <H3 


CH4 


ALCOHOLS  91 

Tetra-hedral  Carbon. — He  assumed  that  carbon  with  its  four  equal 
valencies  exists  in  space  as  though  situated  at  the  center  of  a  regular 
tetra-hedron  with  four  lines  of  valence  each  directed  toward  an  apex. 
If  in  such  an  arrangement  the  atoms  or  groups  linked  to  a  carbon  atom 
to  form  a  molecule  are  all  alike  as  in  the  case  of  methane,  no  other  pos- 
sible form  can  be  given  to  the  molecule  than  that  given  above  in  A. 
If,  however,  as  is  true  in  the  case  of  active  amyl  alcohol  and  of  all  simi- 
lar optically  active  compounds,  the  four  groups  linked  to  a  carbon  atom 
are  all  different  the  suggested  tetrahedral  formula  shows  immediately 
how  two  and  only  two  arrangements  are  possible  as  represented  in  the 
figures  B1  and  B2.  It  will  be  observed  that  the  two  forms  resulting  are 
related  to  each  other  as  the  right  hand  is  to  the  left,  or  as  an  object 
is  to  its  image.  They  are  not  possible  of  being  superimposed  upon 
each  other  and  are  what  Pasteur  termed  enantiomorphic  forms  or 
enantiomorphs. 

Enantiomorphs. — A  molecule  possessing  the  arrangement  in  space 
represented  by  Bl  would,  because  of  its  asymmetry,  be  conceivable  of 
being  unsymmetrical  in  relation  to  polarized  light,  and  could  rotate 
the  plane,  let  us  say,  to  the  right.  A  molecule  arranged  as  in  B2, 
however,  would  necessarily  have  an  opposite  effect  upon  polarized 
light,  i.e.,  it  would  rotate  the  plane  to  the  left.  A  compound  composed 
of  molecules  B1  would  thus  be  dextro-rotatory,  and  one  composed  of 
molecules  B2  would  be  lew-rotatory.  If,  however,  a  compound  was  com- 
posed of  an  equal  number  of  molecules  B1  and  B2  it  would  be  inactive 
to  polarized  light  because  the  effect  of  each  molecule  would  be  bal- 
anced by  the  effect  of  its  counterpart  molecule.  We  would  have, 
therefore,  three  compounds  possessing  exactly  the  same  structure 
but  differing  optically  because  of  the  asymmetric  nature  of  one  of 
the  carbon  atoms  present.  All  compounds,  furthermore,  which 
contained  one  or  more  asymmetric  carbons  would  as  a  result 
be  active  toward  polarized  light,  and  would  exist  in  at  least  these 
three  forms. 

This  then,  is  the  van't  Hoff-LeBel  Theory  of  Stereo-isomerism  known 
also  as  the  Theory  of  the  Asymmetric  Carbon  Atom  or  as  the  Tetrahedral 
Theory.  The  theory  is  supported  by  a  large  number  of  facts  and  has 
been  fruitful  in  leading  to  new  discoveries.  We  shall  find  cases  of 
stereo-isomerism  in  several  of  the  classes  of  compounds  which  we  shall 
study  and  some  of  our  most  common  substances,  such  as  lactic  acid, 


92  ORGANIC  CHEMISTRY 

tartaric  acid  and  the  sugars,  can  be  understood  only  in  the  light  of  this 
theory.  It  is  one  of  the  several  fundamental  conceptions  on  which  the 
whole  structure  of  organic  chemistry  rests.  The  methods  by  which 
the  inactive  form  of  stereo-isomeric  compounds  may  be  separated 
into  its  optical  components  will  also  be  considered  at  length  when  we 
study  tartaric  acid  as  it  was  in  connection  with  his  epoch-making 
investigation  on  this  substance  that  Pasteur  first  made  such  a 
separation. 

Alcohols,  General  Methods  of  Preparation. — The  general  methods 
for  the  preparation  of  the  alcohols,  so  far  as  they  involve  compounds 
which  we  have  already  studied,  resolve  into  one  method  which  has 
been  discussed  already  in  connection  with  the  proof  that  alcohols  are 
hydroxyl  substitution  products  of  the  hydrocarbons.  This  is  the  syn- 
thesis from  alkyl  halides  by  means  of  water  in  the  presence  of  alkalies 
or  in  excess  with  heat  and  by  means  of  moist  silver  oxide,  (AgOH). 

C2H5— (Br  +  H)— OH        >        C2H5— OH  -f  HBr 

Ethyl  bromide  Ethyl  alcohol 

C2H5— (I  +  H)— OH  (+  KOH)     >     C2H5— OH  +  KI  +  2H2O 

Ethyl  iodide  Ethyl  alcohol 

R— (X   +   Ag)— OH        >        R— OH    +    AgX 

Alkyl  halide  Any  alcohol 

This  method,  of  course,  always  yields  the  alcohol  corresponding  to  the 
hydrocarbon  which  is  the  mother  substance  of  the  alkyl  radical  of  the 
halide  used.  The  alcohol  will  contain  the  same  number  of  carbon  atoms 
as  the  alkyl  halide,  and  it  will  possess  the  same  structure.  The  reac- 
tion is  accomplished  in  the  first  case  with  water  by  heating  the  halide 
with  much  water  at  ioo°-2OO°,  the  excess  water  preventing  the  re- 
version of  the  reaction,  or  by  heating  with  water  in  the  presence  of 
alkalies  to  neutralize  the  acid  formed.  With  silver  hydroxide  the 
reaction  takes  place  at  ordinary  temperatures  and  is  non-reversible. 
Lead  hydroxide  may  also  be  used.  As  was  stated  under  the  alkyl 
halides  the  alkyl  iodide  is  the  halide  most  used  because  it  is  the  most 
active. 

General  Properties.— From  Tables  IX  and  X  the  homologous  na- 
ture of  the  series  of  alcohols  can  readily  be  seen  to  be  of  exactly  the 
same  character  as  in  the  case  of  the  hydrocarbons  and  alkyl  halides. 
The  rising  of  the  boiling  point  in  the  normal  series  and  the  falling  in  each 


ALCOHOLS  93 

isomeric  group  holds  here  as  with  alkyl  halides.  The  boiling  points  of 
the  alcohols  compared  with  the  hydrocarbons  is  higher,  the  lowest 
member,  methanol  or  methyl  alcohol,  being  a  liquid  at  ordinary  tem- 
peratures, boiling  at  64.5°.  The  first  three  members,  methyl,  ethyl 
and  propyl  alcohols  are  limpid  liquids  with  a  pleasant  odor  and  burning 
taste,  being  more  or  less  poisonous,  especially  when  concentrated. 
They  burn  readily,  the  lower  members  with  a  colorless  flame.  They 
are  easily  soluble  in  water,  mixing  with  it  in  all  proportions  and  from 
which  they  may  be  separated  by  distillation  or  by  the  addition  of  a 
readily  soluble  salt,  e.g.,  potassium  carbonate  or  calcium  chloride  or  a 
dehydrating  substance  like  quick  lime,  CaO.  As  we  go  up  the  series  the 
boiling  point  rises  and  the  solubility  in  water  decreases.  From  butanol 
to  decanol  they  are  oily  liquids  with  unpleasant  odor,  and  only  the 
first  is  soluble  in  water  in  an  appreciable  amount  (12  parts).  Above 
the  tenth  member  they  are  solid,  wax-like  substances  without  odor, 
insoluble  in  water,  but  soluble  in  ethyl  alcohol  or  ether  from  which 
they  may  be  crystallized. 

Natural  Occurrence. — Alcohols  occur  very  widely  distributed  in 
the  plant  kingdom,  but  not  in  the  free  condition.  It  has  been  claimed 
that  ethyl  alcohol  has  been  found  free  in  plants  but  this  is  doubtful. 
In  combination  with  other  substances,  however,  they  are  found  in 
many  plants  and  also  in  animals.  The  compounds  in  which  they 
occur  are  known  as  esters  or  ethereal  salts  and  are  prepared  by  the 
reaction  of  alcohols  with  organic  acids.  These  compounds  will  be 
discussed  fully  a  little  later.  At  present  it  is  sufficient  to  say  that 
fats,  oils  and  waxes  and  some  of  the  aromatic  or  essential  oil  con- 
stituents of  plants  are  compounds  of  this  kind.  When  these  substances 
are  boiled  with  dilute  alkalies  the  alcohol  is  set  free  and  may  be  ob- 
tained as  such.  We  may  mention  two  examples:  oil  of  winter  green 
yields  methyl  alcohol,  methanol;  spermaceti  yields  cetyl  alcohol, 
hexadecanol.  Besides  being  present  in  this  form  in  plants  and  ani- 
mals, several  of  the  most  important  alcohols  are  obtained  either  by 
direct  distillation  of  vegetable  material,  as  in  the  manufacture  of  methyl 
alcohol  by  the  dry  distillation  of  wood,  or  by  the  distillation  of  the 
product  of  the  fermentation  of  vegetable  materials,  as  in  the  manu- 
facture of  ethyl  and  amyl  alcohols  by  the  fermentation  of  the  sugar 
found  free,  or  formed  from  the  starch,  in  fruit  or  grain. 


94  ORGANIC  CHEMISTRY 

Methyl  Alcohol    Methanol    Wood  Alcohol 
CH3— OH 

Manufacture  from  Wood. — As  its  common  name  signifies  this 
simplest  of  the  alcohols  is  prepared  by  the  dry  distillation  of  wood. 
\yhen  wood  is  heated  out  of  contact  with  oxygen  (air)  carbon  is  left 
in  the  form  of  charcoal  as  one  of  the  products  of  the  decomposition 
of  the  organic  compounds  present  in  the  wood.  The  other  products 
of  the  decomposition  are  volatile  substances  consisting  of  gases  and 
liquids.  The  former  consist  largely  of  hydrocarbons.  The  liquid 
portion  consists  of  a  low  boiling  light  liquid  of  acid  character  and  known 
as  wood  spirits  or  pyro-ligneous  acid,  and  a  high  boiling  thick  liquid 
known  as  wood  tar.  The  pyroligneous  acid,  which  is  also  termed  crude 
wood  vinegar,  contains  several  compounds  in  the  form  of  water  solution. 
The  three  most  important  ones  are  methyl  alcohol)  acetic  acid  and 
acetone.  After  neutralizing  the  acid  by  means  of  an  alkali,  usually 
lime  or  chalk,  the  liquid  is  redistilled.  The  acetic  acid  is  held  back 
as  the  non-volatile  calcium  salt  while  the  methyl  alcohol  with  some  of 
the  other  constituents  distils  over.  Water  is  then  added  to  the  dis- 
tillate in  order  to  separate  out  some  oily  hydrocarbons  and  the  solution 
is  again  distilled.  In  this  last  distillation  a  tall  still,  known  as  a  column 
still,  is  used  by  means  of  which  the  liquid  undergoes  fractionation  and  a 
distillate  is  obtained  containing  a  high  per  cent  of  methyl  alcohol.  The 
best  product  so  obtained  is  known  as  Columbian  Spirits  and  contains 
about  95  per  cent  methyl  alcohol,  the  remainder  being  water  and  traces 
of  other  compounds.  To  secure  absolute  or  100  per  cent  methyl  alco- 
hol the  95  per  cent  product  is  treated  with  calcium  chloride.  With  the 
alcohol,  this  salt  forms  a  crystalline  compound  which  is  separated  and 
purified  and  then  treated  with  sulphuric  acid  and  converted  back  into 
the  alcohol.  A  similar  method  is  to  convert  the  alcohol  into  a  com- 
pound formed  with  oxalic  acid.  This  is  purified  and  then  decomposed 
with  water.  Crude  pyroligneous  acid  usually  contains  about  2  per  cent 
of  methyl  alcohol.  The  wood  used  in  the  manufacture  of  methyl 
alcohol  and  the  other  products  mentioned  is  one  of  the  hard  woods, 
e.g.,  maple,  birch,  beech,  oak  and  hickory.  The  yield  of  alcohol  is 
higher  the  lower  the  temperature  of  distillation.  It  averages  about 
0.5  to  0.8  per  cent.  The  annual  consumption  of  wood  in  this  industry 
in  the  U.  S.  in  1916  was  estimated  at  about  1,100,000  cords.  From  one 


ALCOHOLS  95 

cord  there  is  obtained  about  9.9  gallons  of  82  per  cent  methyl  alcohol 
so  that  the  total  production  was  about  10  to  1 1  million  gallons. 

From  Beet  Sugar  Residues. — Another  source  for  the  manufacture 
of  methyl  alcohol  is  the  residue  from  beet  sugar  manufacture  known  as 
vinasse.  When  beet  sugar  is  refined  the  molasses  from  which  all 
possible  sugar  has  been  crystallized  is  allowed  to  ferment  and  the  liquid 
then  distilled.  The  residue  left  from  this  distillation  is  then  dry  dis- 
tilled and  methyl  alcohol  is  obtained  just  as  from  wood. 

Properties  and  Uses. — Methyl  alcohol  is  a  liquid  of  water-like  ap- 
pearance boiling  at  64.5°  and  with  a  specific  gravity  of  0.812  at  o°. 
In  its  general  properties  it  is  like  ethyl  alcohol  but  is  more  poisonous 
being  often  fatal  if  taken  internally.  It  is  soluble  in  water  in  all  pro- 
portions and  burns  with  a  blue  non-luminous  flame.  It  has  a  charac- 
teristic disagreeable  odor.  Because  of  these  properties  it  is  used  as  a 
denaturant  for  ordinary  alcohol  (p.  100).  It  is  a  good  sol  vent  of  various 
organic  substances  used  in  manufacture  and  the  arts,  e.g.,  shellac,  and 
on  this  account  is  of  great  industrial  value.  It  is  also  used  in  the 
manufacture  of  some  synthetic  dyes. 

Ethyl  Alcohol    Ethanol    Grain  Alcohol 
C2Hff— OH 

Alcoholic  Fermentation. — The  simple  unqualified  name  alcohol 
applies  to  ethyl  alcohol  or  ethanol.  It  has  many  important  industrial 
uses  and  is  of  great  commercial  value.  It  is  formed  by  the  yeast 
fermentation  of  the  sugar  known  as  glucose  or  grape  sugar.  The 
sugar  may  be  present  as  such  in  fruit  juices  or  it  may  be  the  result  of  a 
preceding  fermentation  of  some  other  sugar  or  of  starch.  The  alco- 
hol is  obtained  by  distilling  the  fermentation  liquid.  Many  of  these 
fermentation  liquids  are  used  as  beverages  and  of  one  kind  or  another 
are  found  in  almost  all  countries.  In  such  liquids  in  which  the  alco- 
hol is  present  only  in  quite  dilute  solution  the  compound  has  been 
known  since  ancient  times.  It  was  first  obtained  in  concentrated  pure 
form  in  the  middle  ages,  while  absolute  or  100  per  cent  alcohol  was  first 
made  in  1796  and  its  composition  determined  in  1808. 

Yeast. — It  was  known  that  when  the  juice  of  grapes  or  other  sweet 
fruits  was  allowed  to  ferment  it  took  on  a  sharp  taste  and  affected  the 
body  in  a  stimulating  manner.  In  1836  Cagniard  de  Latour  and  von 
Schwann  showed  that  alcohol  was  produced  by  the  action  of  a  living 


96  ORGANIC  CHEMISTRY 

plant  organism  upon  sugar  solutions.  This  organism  is  the  common 
yeast  plant,  Saccharomyces  ceremssa. 

Catalytic  Theory,  Liebig. — Liebig  held  the  view  known  as  ike-me- 
chanical chemical  theory  of  fermentation  according  to  which  the  action 
is  due  to  some  catalytic  substance. 

Vital  Theory,  Pasteur. — The  views  of  von  Schwann  and  de  Latour 
were  later  thoroughly  established  by  the  work  of  Pasteur  and  it  became 
an  accepted  idea  that  the  life  process  of  the  yeast  plant  is  directly 
connected  with  alcoholic  fermentation.  Yeast  is  able  to  ferment  only 
certain  ones  of  the  common  sugars,  viz.,  glucose  or  grape  sugar  and 
fructose  or  fruit  sugar.  In  the  grape  juice  both  of  these  sugars  and 
the  yeast  plant  also  are  present,  the  latter  occurring  naturally  on  the 
bloom  of  the  grape. 

Enzyme  Theory,  Buchner. — The  recent  work  of  Buchner,  1897 
and  later,  has  shown  that  this  fermentation  is  due  not  to  the  living  action 
of  the  yeast  cell  but  to  a  substance  which  he  called  zymase,  secreted  by  the 
cell.  A  number  of  substances  originally  known  as  ferments  act  cataly ti- 
cally  in  producing  chemical  changes  of  a  similar  nature  and  termed  in 
general  fermentations.  Ptyalin,  the  active  substance  in  saliva,  which 
converts  starch  into  sugar;  maltase,  present  in  intestinal  juice  and  in 
malt,  which  converts  maltose  sugar  into  glucose;  distase,  a  constituent 
of  malted  grain,  which  also  converts  starch  into  maltose  sugar;  and 
pepsin,  the  active  substance  in  gastric  juice  converting  proteins  into 
simpler  compounds;  are  examples  of  these  substances.  Because  al- 
coholic fermentation,  which  is  the  most  common  process  of  this  kind, 
was  supposed,  until  Buchner's  time,  to  be  due  to  a  living  cell,  these  other 
substances  which  could  be  obtained  in  a  more  or  less  pure  condition 
were  distinguished  from  the  yeast  plant  ferment  by  the  name  unor- 
ganized ferment  and  later  as  enzymes  the  alcoholic  ferment  being  known 
as  an  organized  ferment. 

Zymase. — Buchner,  however,  proved  that  the  living  yeast  cell 
could  be  entirely  destroyed  and  an  unorganized  ferment  or  enzyme 
which  he  called  zymase  obtained  from  it  which  in  itself  possessed  the 
power  of  fermenting  grape  sugar.  Thus  alcoholic  fermentation  is  of 
the  same  nature  as  these  other  fermentations  and  is  due,  like  them,  to 
the  catalytic  action  of  an  unorganized  ferment  or  enzyme.  Thus  the 
older  views  of  both  Liebig  and  Pasteur  may  be  considered  as  in  a  way 
true,  i.e.,  the  action  as  Liebig  claimed  is  catalytic,  depending  upon  the 


ALCOHOLS  97 

mere  presence  or  contact  of  the  enzyme,  not  upon  its  mass,  while  the 
living  yeast  cell  is  necessary,  not  directly  to  the  fermentation  itself 
as  Pasteur  claimed,  b.ut  to  the  formation  of  the  enzyme,  a  chemical 
substance  which  actually  produces  the  fermentation.  The  alcoholic 
fermentation  of  sugar,  then,  is  due  to  the  action  of  zymase  which  is 
secreted  by  the  yeast  cell.  In  grapes  both  the  sugar  and  enzyme  are 
present  and  the  juice,  therefore,  ferments  naturally  with  the  formation 
of  alcohol,  the  resulting  alcoholic  liquid  being  known  as  wine.  As 
wine  has  a  considerable  commercial  value  in  itself  it  is  not  the  material 
from  which  pure  or  high  percentage  alcohol  is  obtained. 

Starch  and  Diastase. — The  chemical  substance  which  is  the  ulti- 
mate source  of  industrial  alcohol  is  starch,  or  more  recently  cellulose. 
The  material  from  which  the  starch  is  obtained  is  generally  one  of  the 
cereal  grains  or  potatoes.  Starch,  however,  is  not  acted  upon  by  the 
enzyme  zymase  so  that  it  cannot  be  used  directy  for  the  alcoholic  fer- 
mentation. When  one  of  the  cereal  grains  (or  in  general  any  starch 
containing  seed)  sprouts  or  begins  to  grow  there  is  a  gradual  conversion 
of  the  starch  present  in  the  grain  into  sugar.  This  change  is  brought 
about  by  the  presence  in  the  germinating  grain  of  two  enzymes,  viz., 
diastase  and  maltase.  The  diastase  converts  the  starch  into  a  sugar 
known  as  maltose  and  maltase  converts  the  maltose  into  glucose. 
When,  therefore,  these  enzymes  have  acted  upon  the  starch  it  is  converted 
into  a  sugar  upon  which  the  alcoholic  enzyme  zymase  can  act.  In 
practice  the  grain,  usually  corn,  rye,  or  barley  is  allowed  to  sprout  in 
a  warm  room,  6o°-62°,  ground,  and  water  added  making  a  thin  mush 
or  mash.  This  is  next  treated  with  yeast  and  allowed  to  stand  at  about 
25°.  Temperatures  above  33°  are  injurious  to  the  enzyme.  After 
fermentation  the  mash  or  wort,  as  it  is  now  called,  is  either  placed  in  re- 
torts and  the  alcohol  distilled  off  directly  or  the  liquid  of  the  wort  is 
separated  by  nitration.  The  amount  of  alcohol  present  in  the  wort  is 
usually  about  5  per  cent  but  in  wines  it  may  go  as  high  as  14  per  cent. 
Above  this  it  cannot  go  because  a  stronger  solution  of  alcohol  is  de- 
structive to  the  enzyme.  The  distillation  of  the  alcoholic  liquid  takes 
place  in  a  tall  still,  known  as  a  column  still,  with  many  condensing 
plates  so  that  the  alcoholic  vapor  is  continually  condensed  and  redis- 
tilled (fractionated).  By  a  direct  distillation  from  such  an  apparatus 
a  solution  of  alcohol  is  obtained  of  about  90  per  cent.  This  may  con- 
tain small  amounts  of  the  higher  boiling  alcohols  present  (propyl  and 


98  ORGANIC  CHEMISTRY 

amyl  alcohols).  The  non- volatile  substances  present  in  the  fermenta- 
tion liquid,  the  principal  ones  being  glycerol  and  succinic  acid,  are  left 
behind  in  the  retort.  For  the  still  greater  purification  of  the  alcohol 
it  is  first  mixed  with  water  making  about  a  50  per  cent  solution.  This 
allows  the  separation  of  some  of  the  amyl  alcohols  as  an  oily  layer.  It 
is  now  distilled  again  through  a  rectifying  or  column  still.  By  this 
second  distillation  the  purest  and  strongest  alcohol  of  commerce  is 
obtained.  It  is  about  95  per  cent  and  is  known  as  Cologne  Spirits. 

Absolute  Alcohol. — For  the  preparation  of  absolute  or  100  per  cent 
alcohol  the  95  per  cent  product  is  placed  over  lime,  CaO,  and  after 
standing  or  heating  with  a  return  condenser  to  allow  the  lime  to  re- 
move all  water,  the  whole  mass  is  heated  and  alcohol  distils  over  as 
100  per  cent.  Anhydrous  copper  sulphate  may  also  be  used  as  a  de- 
hydrating agent,  but  this  is  common  only  in  laboratories  and  not  in 
commercial  practice. 

Properties  and  Uses. — The  physical  and  chemical  properties  of 
ethyl  alcohol  are  similar  to  those  of  methyl  alcohol,  only  it  has  a  higher 
melting  point  and  boiling  point  in  accord  with  its  relation  in  the  homol- 
ogous series.  It  boils  at  78°  and  melts  at  —130°,  specific  gravity 
0.806  (o°).  It  is  a  clear,  water-like  liquid  with  a  pleasant  pungent  odor. 
It  is  poisonous  in  concentrated  form,  but  in  dilute  condition  as  it  occurs 
in  beverages,  it  possesses  stimulating  effects.  It  burns  with  a  blue 
flame.  Its  solvent  action  is  similar  to  that  of  methyl  alcohol  though 
stronger  toward  organic  substances.  It  also  dissolves  alkalies.  It 
forms  crystalline  salts  which  contain  alcohol  of  crystallization,  e.g.: 

KOH.2C2H5OH  LiC1.4C2H5OH 

MgCl2.6C2H5OH  CaCl2.4C2H5OH 

Absolute  alcohol,  because  of  its  affinity  for  water,  acts  as  a  dehydrating 
agent,  and  is  used  to  remove  the  last  traces  of  water  from  some  sub- 
stances, especially  animal  and  plant  tissues.  It  cannot,  therefore, 
be  kept  except  in  bottles  well  stoppered. 

Alcoholic  Beverages 

The  use  of  alcoholic  beverages  is  an  ancient  and  very  general  cus- 
tom. The  natural  alcoholic  beverages  are  those  weak  in  alcohol  con- 
tent and  are  simply  the  undistilled  fermentation  liquids.  They  are 
wine,  beer,  alet  stout,  and  others  similar  in  character  but  with  different 


ALCOHOLS  99 

names.  Wine  is  the  simple  fermented  grape  juice  and  contains  between 
7  per  cent  and  20  per  cent  alcohol.  Those  above  14  per  cent  are 
termed  fortified  wines  because  they  have  alcohol  added  to  them.  Beer, 
ale  and  stout  are  fermented  liquors  obtained  by  filtering  or  decanting 
off  the  fermented  liquid  from  barley  made  in  the  general  manner 
described  in  the  manufacture  of  alcohol.  These  are  still  lower  in  alcohol 
content  than  wine,  being  between  2  per  cent  in  pale  beers  and  $  or  6 
per  cent  in  ales  and  porters.  The  characteristic  taste  or  flavor  of  wines 
and  the  names  given  to  them  depend  upon  the  variety  of  grape  used, 
the  locality  where  the  wine  is  made,  or  the  particular  processes  in- 
volved in  its  manufacture.  The  same  general  facts  determine  the 
quality  and  name  of  the  beers  and  ales.  When  a  fermented  mash 
prepared  from  grain  or  from  fruits  or  molasses  is  distilled  without 
attempting  to  secure  complete  purification  of  the  distillate  or  the  high- 
est per  cent  of  alcohol  possible  a  distillate  is  obtained  possessing  cer- 
tain characteristic  properties  due  to  the  original  material  used.  These 
liquids  constitute  the  distilled  liquors  known  as  whisky,  brandy, 
cognac,  gin,  rum,  etc.  These  liquors  contain  from  35  per  cent  to  40 
per  cent  alcohol. 

Industrial  Alcohol 

The  greatest  importance  of  alcohol  is  not,  however,  in  its  use  in  one 
of  these  various  forms  as  a  beverage,  but  in  its  wide  application  in  the 
arts  as'a  solvent  or  as  a  substance  from  which  other  valuable  compounds 
are  made.  In  some  of  its  industrial  uses  it  may  be  replaced  by  its 
methyl  homologue,  but  not  in  all,  at  least  to  advantage.  In  its  syn- 
thetic uses  it,  of  course,  cannot  be  replaced  by  the  other.  Because  of 
its  use  in  beverages  which  are  almost  wholly  luxuries,  nearly  all  civilized 
countries  have  considered  alcohol  a  proper  article  for  taxation  and  for 
government  control. 

Government  Regulation  and  Tax.— The  tax  is  usually  high  so  that 
the  cost  of  pure  alcohol  is  far  above  the  cost  of  actual  manufacture. 
Alcoholic  beverages  and  high  per  cent  alcohol  that  are  subject  to  such 
taxation  are  taxed  according  to  the  amount  of  pure  alcohol  present. 
It,  therefore,  becomes  necessary  to  determine  the  strength  of  alcoholic 
liquids,  and  also  to  have  a  fixed  standard  of  strength. 

Proof  Spirit. — The  standard  of  strength  upon  which  alcohol  is 
taxed  is  not,  as  might  seem  natural,  100  per  cent  or  absolute  alcohol, 


100  ORGANIC  CHEMISTRY 

but  something  less  than  this.  In  this  country  the  standard  strength  is 
that  of  an  alcohol- water  solution  of  50  per  cent,  by  volume,  or  42.7  per 
cent,  by  weight.  In  Great  Britain  it  is  57.1  per  cent,  by  volume  or 
49.3  per  cent,  by  weight.  This  is  termed  proof  spirit  and  tax  is 
always  made  according  to  per  cent  proof  spirit.  The  analysis  of  such 
liquids  for  alcohol  per  cent  has  had  much  attention  paid  to  it  in  order  to 
make  the  methods  reliable  and  applicable  to  every  varying  condition. 
The  general  method  is  to  take  a  definite  amount  of  the  liquid  (100  cc.), 
which  will  be  smaller  the  stronger  the  liquid,  dilute  to  a  definite  volume 
(150  cc.)  and  then  distil  off  two-thirds  (100  cc.).  The  distillate  con- 
tains the  entire  amount  of  alcohol  present  in  the  liquid  and,  in  case 
necessary  precautions  have  been  taken,  only  water  in  addition.  Mix- 
tures of  pure  water  and  alcohol  possess  a  definite  specific  gravity  for 
each  variation  in  concentration,  see  Table  XI,  so  that  the  determina- 
tion of  the  specific  gravity  of  the  distillate  defines  the  exact  amount  of 
alcohol  present.  As  this  is  the  entire  amount  present  in  the  original 
liquid  we  have  an  exact  determination  of  the  factor  desired. 

Denatured  Alcohol. — Because  of  the  high  tax  (U.  S.  tax:  $1.10 
per  proof  gal.  in  1914,  $2.20  in  1920)  and,  therefore,  the  high 
price  of  ethyl  alcohol,  and  also  because  of  the  fact  that  methyl  alcohol, 
which  has  no  tax,  cannot  always  be  substituted  for  it,  it  is  of  the  utmost 
importance  that  alcohol  which  is  to  be  used  industrially,  not  as  a 
beverage,  should  be  removed  from  taxation  and  thus  greatly  cheapened 
in  price.  Germany  and  England  have  had  laws  in  operation  for  some 
time,  removing  the  tax  on  industrial  alcohol  but  it  was  not  until  1906 
that  the  United  States  had  a  law  of  this  kind.  In  order  to  make  this 
removal  from  taxation  possible  it  is  necessary  to  render  the  alcohol  for 
industrial  uses  unfit  for  beverage  purposes.  Alcohol  so  treated  is  termed 
denatured,  denaturing  being  accomplished  by  the  addition  of  some 
substance  which  does  not  interfere  with  the  use  of  the  alcohol  industrially 
but  makes  it  unfit  for  internal  consumption.  For  example,  alcohol  to  be 
used  in  the  manufacture  of  ether  is  denatured  by  the  addition  of 
sulphuric  acid  which  is  the  reagent  necessary  when  the  ether  is  made. 
For  ordinary  solvent  purposes  the  denaturant  is  usually  methyl  alco- 
hol, while  a  little  pyridine  is  often  used  to  give  it  an  offensive  odor,  and 
sometimes  a  dye  is  added  to  give  a  noticeable  color.  The  denatured 
alcohol  law  has  two  advantages.  It  cheapens  the  cost  of  alcohol  so 
that  things  made  by  its  use  can  be  likewise  cheapened.  It  also  makes  it 


ALCOHOLS 


101 


possible  to  manufacture  the  alcohol  more  generally  and  to  use  in  its 
manufacture  a  great  many  starch,  sugar  or  cellulose  containing  ma- 
terials which  have  heretofore  been  simply  waste  products  of  the  farm. 
The  substances  generally  used  are  fruit,  most  vegetables,  especially 
potatoes,  inferior  grain,  sawdust,  etc. 

TABLE  XL — ETHYL  ALCOHOL 

Alcohol  in  Per  cent  by  Volume,  Corresponding  to  Specific  Gravity  at  — '—TO  of 
Mixtures  of  Water  and  Alcohol.     (From  Landolt's  Tables,  p.  226) 


,  15.56° 

rfiiis* 

Volume 
per  cent 
alcohol 

15-56° 

Volume 
per  cent 
alcohol 

^  I5.560 

Volume 
per  cent 
alcohol 

dl5-56° 

di5.56° 

i  .000 

O 

0.9709 

25 

0.8773 

75 

0.9985 

I 

0.9970 

2 

0-9655 

30 

0.8639 

80 

0.9956 

3 

0.9942 

4 

0.9592 

35 

0.8496 

85 

0.9928 

5 

0.9915 

6 

0.9519 

40 

0-8339 

90 

0.9902 

7 

o  .  8306 

9i 

0.9890 

8 

0-9435 

45 

0.8272 

92 

0.9878 

9 

0.8237 

93 

0.9866 

10 

0-9343 

SO 

0.8201 

94 

0.9854 

ii 

0.8164 

95 

0.9843 

12 

0.9242 

55 

0.8125 

96 

0.9832 

13 

o  .  8084 

97 

0.9821 

14 

0.9134 

60 

0.8041 

98 

0.9811 

15 

0.7995 

99 

0.9021 

65 

0.7946 

IOO 

0.9760 

20' 

o  .  8900 

70 

Amyl  Alcohols    Pentanols    Fusel  Oil 
C5H9— OH 

Fusel  Oil. — In  the  first  distillation  of  alcohol  from  fermented  liquids 
there  is  always  present  in  the  distillate  a  small  amount  of  the  higher 
alcohols.  The  mixture  of  these  alcohols  which  may  be  separated  from 
the  ethyl  alcohol  is  known  as  fusel  oil.  It  contains  some  or  all  of  these 
compounds:  propanol-i,  butanol-i,  2-methyl  propanol-i,  2-methyl 


102  ORGANIC  CHEMISTRY 

propanol-2,  pentanol-i,  2-methyl  butanol-4,  2-methyl  butanol-i, 
pentanol-2,  2-methyl  pentanol-5,  2-methyl  hexanol-6.  In  the  manu- 
facture of  distilled  liquors  some  fusel  oil  always  goes  over  with  the  dis- 
tillate and  is  contained  in  the  liquor.  It  is  probably  this  which  gives 
to  brandy  and  similar  liquors  their  especially  injurious  effects.  The 
fusel  oil  is  also  known  as  crude  amyl  alcohol,  the  two  amyl  alcohols 
called  active  amyl,  2-methyl  butanol-i,  and  inactive  amyl,  2-methyl 
butanpl-4,  being  the  two  chief  constituents.  Because  these  two  amyl 
alcohols  are  found  in  the  fermentation  liquids  they  are  known  together 
as  fermentation  amyl  alcohol. 

DERIVATIVES  OF  ALCOHOLS 

i.  ESTERS  OR  ETHEREAL  SALTS 

R— (ACID  R) 

Esters  or  ethereal  salts  are  derivatives  of  alcohols  formed  by  the 
reaction  of  an  alcohol  with  an  acid.  As  they  are  thus  acid  derivatives 
also  and  as  the  more  important  esters  are  those  formed  from  the  or- 
ganic acids,  which  we  shah1  soon  study,  the  chief  discussion  of  them  as  a 
group  will  come  later.  There  are,  however,  to  be  considered  the  esters 
formed  from  inorganic  acids  and  these  will  be  presented  now.  The 
chemical  properties  of  alcohol  in  its  relation  to  both  bases  and  acids 
are  of  especial  interest  and  importance.  We  have  spoken  of  the  fact 
that  alcohol  as  an  hydroxyl  compound  belongs  to  the  water  type,  and 
that  the  other  representatives  of  this  type  are  the  metal  hydroxides  or 
bases,  and  the  non-metal  hydroxides  or  acids, 

Sodium  hydroxide  Na — OH  base 

Water  H— OH  neutral 

Alcohol  C2H6— OH 

Phosphorous  acid  P  =  (OH)3  acid 

Now  we  know  that  while  water  stands  as  it  were  on  the  dividing  line 
between  metal  and  non-metal  hydroxides,  and  is  a  perfectly  neutral 
compound,  there  are  other  hydroxides  which  may  be  placed  on  either 
side,  i.e.,  they  may  form  either  bases  or  acids.  The  elements  whose 
hydroxides  are  of  this  nature  may  be  illustrated  by  the  element 
aluminium.  Toward  strong  bases  aluminium  hydroxide  acts  as  an  acid 
and  forms  salts  in  which  the  aluminium  plays  the  part  of  a  non-metal, 


DERIVATIVES    OF   ALCOHOLS — ESTERS  103 

but  toward  strong  acids  it  acts  like  a  base,  forming  salts,  of  aluminium 
as  a  metal. 

As  an  acid,  A1(OH)3    +    NaOH        »        AlO-ONa  +   2H2O 

Aluminium  Sodium 

hydroxide  aluminate 

As  a  base,  A1(OH)3     +     HC1  -»        A1C1,    +     3H2O 

Aluminium  Aluminium 

hydroxide  chloride 

Alcohol  a  Base  or  an  Acid. — Now  alcohols  are  similar  to  aluminium 
hydroxide  in  their  property  of  reacting  withjboth  bases  and  acids,  as 
follows : 

C2H5— OH  +  NaOH    >    C2H5— ONa    +    H20 

Alcohol  Sodium  alcoholate 

C2H6— OH  +  HC1        — ->        C2H5— Cl  +  H2O 

Alcohol  Ethyl  chloride 

With  sodium  hydroxide  or  better  with  sodium,  alcohol  forms  sodium 
alcoholate,  a  salt  in  which  the  ethyl  radical  plays  the  part  of  anon-metal, 
while  with  hydrochloric  acid  it  forms  ethyl  chloride,  a  salt  in  which 
the  ethyl  radical  plays  the  part  of  a  metal.  Now  while  alcohol  acts  as 
an  acid  toward  only  the  strong  bases  it  acts  as  a  base  toward  practically 
all  acids.  We  may  say  then  that  the  basic  character  of  alcohol  is  more 
pronounced  than  the  acid.  In  both  of  these  cases  we  have  reactions 
that  are  simply  the  neutralization  of  an  acid  or  a  base  by  a  base  or 
an  acid,  the  products  being  the  same  as  in  all  neutralizations,  viz., 
a  salt  and  water.  Both  sodium  alcoholate  and  ethyl  chloride  are  to 
be  looked  upon  then  as  salts. 

Esters  or  Ethereal  Salts. — The  metal  salts  of  alcohol  are  not  of 
special  importance,  but  the  ethyl  salts  of  acids  are  extremely  important 
compounds.  These  salts  in  which  the  ethyl  radical  acts  as  a  metal  are 
called  esters  or  ethereal  salts.  While  the  name  ethereal  salt  is  perhaps 
the  best  and  most  significant,  as  it  indicates  the  salt  character  of  the 
compound,  the  name  ester  will  be  used  as  it  has  been  generally  adopted. 
The  reaction  given  is  a  general  reaction  of  alcohols.  The  general 
formula  for  ester  being  R — (Acid  R)  or  an  alkyl  radical  joined  to 
an  acid  radical. 

In  the  case  of  tjhe  halogen  acids  which  are  binary  acids  or  non-oxygen 
acids  the  esters  are  the  same  as  the  alkyl  halides,  i.e.,  halogen  substitu- 
tion products  of  the  hydrocarbons.  With  the  oxygen  acids,  e.g.,  nitric, 
sulphuric,  etc.,  the  esters  are  not  simple  substitution  products  of  hydro- 
carbons. With  these  inorganic  acids  which  contain  oxygen  the  acid 


I04  ORGANIC  CHEMISTRY 

radical  is  usually  considered  as  that  part  of  the  acid  without  the 
hydroxyl  hydrogen  and  the  general  formula  for  ester  R  —  (Acid  R) 
holds.  With  the  organic  acids  which  also  contain  a  hydroxyl  group 
the  acid  radical  does  not  include  the  hydroxyl  oxygen  and  the  general 
formula  for  such  esters  becomes  R—  O—  (Acid  R).  This  will  be  made 
clear  later.  With  ethyl  alcohol  again  as  our  illustration,  the  esters 
of  nitrous,  nitric  and  sulphuric  acids  are  formed  as  follows: 
C2H5—  (OH  +  H)O—  NO  <  --  >  C2H5—  O—NO  +  H20 

Alcohol  Nitrous  acid  Ethyl  nitrite 

C2H5—  (OH  +  H)O—  NO2  <  --  >    C2H5—  O—  N02  +  H20 

Nitric  acid  Ethyl  nitrate 

C2H5—  (OH  +  H)0—  SO2OH         <  --  »     C2H5—  O—  S02OH  +  H2O 

Sulphuric  acid  Ethyl  hydrogen  sulphate 

Ethyl  acid  sulphate 

C2H5—  (OH         H)O 

C2Hb—  0—  SO 
C2H5—  (OH 


or  >S02    +    2H20 


Ethyl  sulphate 

As  sulphuric  acid  is  dibasic  it  forms  two  kinds  of  esters,  one  acid  and 
one  neutral.  These  are  analogous  to  the  acid  and  neutral  salts  that 
are  formed  when  sulphuric  acid  is  neutralized  with  sodium  hydroxide. 
In  the  same  way  alcohols  form  mono-,  di-  and  tri-alkyl  esters  with  phos- 
phoric acid  analogous  to  the  mono-,  di-,  and  tri-basic  salts  of  sodium  and 
phosphoric  acid.  The  esters  of  nitrous  acid  are  isomeric  with  the 
nitro  substitution  products  of  the  hydrocarbons  (p.  74).  The  two 
classes  of  compounds  are,  however,  distinctly  different.  The  nitro 
compounds  formed  by  the  reaction  between  an  alkyl  halide  and  silver 
nitrite,  have  the  nitro  group  (  —  NO2)  substituted  for  a  hydrogen  of  the 
hydrocarbon,  e.g.,  C2H5  —  NO2.  In  these  the  nitrogen  is  linked  di- 
rectly to  the  carbon  as  shown  by  their  reduction  to  amino  compounds. 
On  the  other  hand,  the  isomeric  nitrous  acid  esters  are  formed  by  the 
reaction  given  above  between  an  alcohol  and  nitrous  acid.  In  these 
esters  the  group  (  —  O  —  NO)  replaces  the  hydroxyl  of  the  alcohol  and 
the  union  of  the  nitrogen  is  not  directly  with  the  carbon  but  through  an 
intervening  oxygen  atom,  C2Hs  —  O  —  NO.  Furthermore  the  esters  are 
easily  decomposed  by  water  yielding  the  alcohol  while  the  nitro  compounds 
are  not  thus  decomposed  by  water. 


ETHERS  105 

Properties. — This  easy  decomposition  by  water,  especially  in  the 
presence  of  alkalies,  is  a  characteristic  property  of  esters.  Because  of 
this  fact  the  reaction  for  the  formation  of  an  ester  reverses  when  the 
concentration  of  the  water,  which  is  the  other  product  of  the  reaction, 
becomes  strong  enough.  The  reaction  is  therefore  written  with  double 
arrows  to  indicate  its  reversible  nature.  When  such  reversal  of  the 
reaction  occurs  the  alcohol  is  again  formed.  This  was  mentioned  in 
connection  with  the  synthesis  of  alcohols  from  alkyl  halides  (p.  92). 
The  first  part  of  the  name,  ethereal  salt,  is  derived  from  their  general 
character  as  more  or  less  volatile  and  pleasant  smelling  substances. 
This  applies  especially  to  the  esters  formed  with  the  organic  acids  which 
we  shall  soon  consider.  It  is  also  among  these  esters  of  the  organic 
acids  that  we  find  the  most  important  representatives  of  the  group 
and  those  which  are  found  most  widely  distributed  in  plants  and  animals. 

2.  ETHERS  R— O— R 

The  importance  of  the  esters  of  ethyl  alcohol  and  sulphuric  acid  is 
in  connection  with  the  formation  of  the  compounds  we  shall  now  take 
up,  viz.,  ethers. 

Synthesis. — The  salts  of  strong  metals  with  alcohols  we  have  shown 
are  represented  as  CH3 — ONa,  C2H5 — ONa,  etc.  When  an  alkyl 
halide  acts  upon  these  compounds  one  of  the  products  is  a  substance 
known  as  an  ether,  the  other  product  is  the  sodium  halide.  The  reac- 
tion must  be  then,  in  the  case  of  ethyl  alcohol: 

C2H5— O(Na  +  1)— C2H5    >    C2H5— O— C2H5  +  Nal 

Sodium  alcoholate        Ethyl  iodide  Ethyl  ether 

Williamson's  Synthesis. — This  reaction  is  known  as  Williamson's 
synthesis  because,  in  1851,  he  showed,  by  it,  the  true  constitution  of 
ether,  and  made  possible  the  explanation  of  its  preparation  from  alco- 
hol and  sulphuric  acid  as  given  a  little  later  on.  The  reaction  is  similar 
to  the  Wurtz  reaction  between  sodium  and  an  alkyl  halide  by  which  a 
hydrocarbon  is  formed. 

CH3— (I  +  2Na  +  I)— CH3        — >     CH3— CH3  +  2NaI 

The  constitution  of  ether  seems  to  be  well  established  simply  by  this 
one  reaction  which  in  general  is 

R— 0— (Na    +    I)— R        — »     R— O— R    +    Nal 

Sodium  alcoholate  Alkyl  An  ether 

halide 


106  ORGANIC  CHEMISTRY 

A  second  synthesis  of  ethers  proves  again  that  their  constitution  is 
that  of  an  oxide  of  an  alkyl  radical.  When  an  alkyl  halide  is  heated 
with  dry  silver  oxide,  Ag20,  an  ether  is  formed: 

2C2H6— (I  +  Ag2)O    >    (C2H6)2  =  O  or  C2HB— O— C2H5  +  2AgI 

Ethyl  iodide  Ethyl  ether 

As  alcohols  have  been  shown  to  be  'hydroxides  so  the  ethers,  by  these 
syntheses,  are  oxides,  for  the  sodium  which  in  sodium  ethylate  has  re- 
placed the  hydroxyl  hydrogen  of  the  alcohol  is,  in  ether,  replaced  by  a 
second  alkyl  radical.  The  following  formulas  may  make  these  re- 
lationships plain. 

Sodium  hydroxide     Na — O — H  Na — O — Na          Sodium  oxide 

Alcohol  C2H5— O— H        C2H5— O— C2H5       Ethyl  ether 

(ethyl  hydroxide)  (ethyl  oxide) 

Simple  Ethers  and  Mixed  Ethers 

Just  as  there  is  an  homologous  series  of  alcohols  so  there  is  also  an 
homologous  series  of  ethers,  each  alcohol  having  a  corresponding  ether. 
Thus  we  have  methyl  ether,  CH3— O— CH3,  propyl  ether,  CsH?— O 
— CsH.7,  etc.  As  by  the  Wurtz  synthesis  of  hydrocarbons  we  can 
theoretically  unite  any  radical  with  any  other  radical  by  heating  the 
iodide  of  one  with  the  iodide  of  the  second  in  the  presence  of  sodium, 
so  by  the  Williamson  synthesis  we  should  be  able  to  form  ethers  by 
uniting  any  radical  with  any  other  radical  through  the  oxgyen  of  the 
sodium  alcoholate.  The  formula  for  ethers  then,  R — O — R,  may  be 
written  R — O — R',  in  which  R  and  R'  may  be  the  same  or  may  be  differ- 
ent. Ethers  in  which  they  are  the  same  are  called  simple  ethers,  and 
when  they  are  different  the  ethers  are  called  mixed  ethers. 

Names  of  Ethers. — The  systematic  official  names  of  ethers  are  made 
by  using  the  term  oxy  in  connection  with  the  hydrocarbon  names 
corresponding  to  the  alkyl  radicals.  The  common  names  are  the  same 
as  the  alcohols  with  ether  in  place  of  alcohol.  The  following  table 
gives  some  of  the  better  known  ethers  of  both  kinds  and  will  illustrate 
the  nomenclature. 

Isomerism. — The  isomerism  of  the  ethers  may  be  due  to  several 
things.  Referring  to  Table  XII  we  see  that  in  simple  ethers  it  may  be 
due  to  isomerism  of  the  alkyl  radicals  as  in  propyl  ether  and  in  iso- 
propyl  ether.  In  mixed  ethers  two  different  sets  of  alkyl  radicals  yield 


ETHERS 


107 


.     ro  O 

PQ      (N      CO    ON 


00     CO    M- 
CO  <O     10 


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S 

s  ; 

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ci  —  o 

o  W 

u 

'..  —  ETHERS 
Ethers 

CH3—  O—  CH3  
C2H5—  0—  C2H5 
CHs—  CH2—  CH2—  O— 
CHs—  CH—  O—  HC—  C 

1  1 
CH3  CHS 

Ethers 

CH3—  0—  C2H5 
CHr-  O—  C3H7  

L-aHr-  O-  Call  7  
C2H5—  O—  HC—  CH3.  .  . 

1 

CH3 
CH3—CH2—  CHr-0-: 

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!08  ORGANIC  CHEMIS1RY 

someric  ethers  as  in  methane-oxy-i -propane  and  methane-oxy-2- 
propane.  Also  a  mixed  ether  may  be  isomeric  with  a  simple  ether  as 
methane-oxy-propane  and  ethane-oxy-ethane  or  propane-oxy-rpo- 
pane  and  propane-i-oxy-2-propane. 

Class  Isomerism. — We  have  also  with  the  ethers  a  new  case  of  iso- 
merism  different  from  any  we  have  studied.  It  will  be  seen  on  ex- 
amining the  empirical  formulas  of  ethers  that  they  are  the  same  as  the 
alcohols  with  an  equal  number  of  carbon  atoms. 

C2H6O    Methyl  ether,    CH3— O— CH3    Ethyl  alcohol,    C2H5— OH 
C4HioO    Ethyl  ether,    C2H5— O— C2H5    Butyl  alcohol,    C4H9— OH 

Here  isomerism  is  not  due  to  difference  in  structure  in  compounds  of 
the  same  class  but  to  difference  in  the  class  to  which  compounds  of  the 
same  composition  belong.  Such  isomerism  may  be  called  class  isomerism 
and  is  a  form  of  structural  isomerism. 

Chemical  Properties. — Chemically  the  ethers  are  not  very  active 
nor  do  they  lead  to  important  derivatives.  Chlorine  forms  substitu- 
tion products  in  which,  as  in  methyl  ether,  one  to  six  hydrogens  of  the 
alkyl  radicals  are  substituted.  The  halogen  acids,  especially  hydriodic 
acid,  form  an  alcohol  by  a  reaction  analogous  to  the  reversion  of  the 
Williamson  synthesis. 

C2H5— O— C2H5  +  H— I        >        C2H6— OH  +  C2H5— I 

Ethyl  ether  Alcohol  Ethyl  iodide 

Ethyl  Ether    C^s— O— C2H5    Ethane-oxy-Ethane 

The  most  important  ether  of  the  whole  group  is  ethyl  ether  which 
is  the  common  ether  of  commerce,  the  formula  of  which  is  C2H5 — O — 
C2H5.  This  ether  may  be  prepared  by  either  of  the  syntheses  given 
above.  These  are  not,  however,  the  methods  used  in  preparing  it  on 
the  large  scale.  The  commercial  process  is  as  follows : 

Commercial  Manufacture. — Alcohol  and  sulphuric  acid  are  mixed 
in  the  proportion  of  one  molecule  of  alcohol  to  one  molecule  of  sulphuric 
acid.  This  is  in  the  proportion  of  46  grams  alcohol  (molecular  mass  of 
alcohol  equals  46)  to  98  grams  sulphuric  acid  (molecular  mass  equals 
98)  or  approximately  one  part  alcohol  (absolute)  by  weight  to  two 
parts  sulphuric  acid  (concentrated)  by  weight.  This  will  be  found 
to  be  approximately  in  the  proportion  of  one  volume  alcohol  to  one 
volume  sulphuric  acid.  After  cooling  the  well  shaken  mixture  it  is 


ETHERS 


109 


heated  to  140°  and  when  this  temperature  is  reached  fresh  alcohol  is 
added  slowly  through  a  tube  reaching  below  the  surface  of  the  mixture. 
As  alcohol  is  added  ether  distils  over,  and  as  long  as  fresh  alcohol  is 
added  ether  is  formed,  in  an  amount  equivalent  to  the  alcohol  added, 
two  molecules  of  alcohol  yielding  one  molecule  of  ether.  This  operation 
may  be  continued  indefinitely.  The  explanation  of  this  reaction  was 
first  made  clear  by  Williamson  and  is  as  follows:  When  alcohol  and 
sulphuric  acio^  react,  in  the  proportion  of  one  molecule  of  each,  ethyl 
sulphuric  acid  is  formed. 

C2H5— (OH  +  H)O— SO2— OH    >    C2H5— O— SO2— OH  +  H2O 

Alcohol  Sulphuric  acid  Ethyl  sulphuric  acid 

This  may  be  isolated  as  an  easily  soluble  crystalline  compound,  also 
in  the  form  of  its  barium  or  calcium  salts  by  neutralizing  the  remaining 
acid  hydrogen  with  barium  or  calcium  hydroxide. 

2C2H5— O— S02— OH  +  Ba(OH)2        > 

Ethyl  sulphuric  acid 

(C2H5— O— SO2— O)2Ba  +  2H2O 

Barium  ethyl  sulphate 

When  ethyl  sulphuric  acid  is  boiled  with  water  it  acts  as  do  esters 
in  general.  The  reaction  of  its  formation  is  reversed  and  alcohol  and 
sulphuric  acid  are  reformed. 

C2H5— (OSO2OH  +  H)OH        >        C2H5— OH  +  HO— SO2— OH 

Ethyl  sulphuric  acid  Alcohol  Sulphuric  acid 

Now  in  the  first  stage  of  the  preparation  of  ether,  ethyl  sulphuric 
acid  is  formed.  When  this  is  heated  to  140°  and  fresh  alcohol  is  added 
the  reaction  is  analogous  to  that  between  ethyl  sulphuric  acid  and  water, 
ether  is  formed  and  sulphuric  acid  is  regenerated. 

C2H5— (OS02OH  +  H)0— C2H0        > 

Ethyl  sulphuric  acid 

C2H5— O— C2H5  +  HO— SO2— OH 

Ether  Sulphuric  acid 

This  sulphuric  acid  then  unites  with  more  alcohol  forming  ethyl  sul- 
phuric acid  which  again  reacts  with  alconol  and  yields  ether  and  sul- 
phuric acid.  Thus  the  sulphuric  acid  remains  in  the  reaction  mixture 
either  as  ethyl  sulphuric  acid  or  as  free  sulphuric  acid.  It  acts  as  a 
carrier  of  the  ethyl  radical  or  it  is  perhaps  better  to  say  as  a  dehydrating 
agent  removing  the  water  which  is  the  other  product  of  the  first  step 
in  the  reaction.  We  have  said  that  the  reaction  goes  on  indefinitely. 


1  10  ORGANIC  CHEMISTRY 

This  is  not  strictly  true  because  the  water  formed,  though  partly  re- 
moved by  distillation,  gradually  dilutes  the  acid  until  it  is  too  weak  to 
react  with  the  alcohol,  i.e.,  until  the  reversible  reaction  occurs  and  the 
ethyl  sulphuric  acid,  as  fast  as  it  is  formed,  is  decomposed  again  into 
alcohol  and  sulphuric  acid.  Also  the  heat  of  the  reaction  gradually 
uses  up  the  acid  owing  to  its  reduction  by  means  of  the  alcohol. 

Ether  the  Anhydride  of  Alcohol.  —  On  examination  of  the  double 
reaction  it  is  seen  that,  in  effect,  the  result  has  been  to  remove  one  mole- 
cule of  water  from  two  molecules  of  alcohol.  The  hydroxyl  is  taken  from 
one  alcohol  molecule  and  the  hydrogen  from  the  other.  We  may  represent 
the  combined  reaction  as  one. 


C2H5—  (OH      H) 

+  I  -**>  3  +  H2O  +  HO—  S02—  OH 

C2H5—  O(H      O—  S02OH  CzHs 

Alcohol  Sulphuric  acid  Ether  Sulphuric  acid 

In  fact,  of  course,  the  hydrogen  from  the  second  molecule  of  alcohol 
goes  to  re-form  sulphuric  acid,  but  as  it  simply  replaces  the  hydrogen 
given  by  the  acid  to  form  water  with  the  alcoholic  hydroxyl  of  the  first 
molecule  of  alcohol  the  result  is  in  effect  as  we  have  stated.  This  means 
then  that  ether  is  the  anhydride  of  alcohol  and  their  relation  to  each  other 
is  analogous  to  that  between  metal  and  non-metal  hydroxides  and  oxides. 

C2H5—  (OH  -C2H5v 

-*  )>O  +  H20 

C2H5—  O(H  C2H6 

Alcohol  Ether 

Na—  (OH  Na 

—  >  \)  +  H2O 

Na—  0(H  NaX 

Sodium  hydroxide  Sodium 

oxide 

This  agrees  with  the  constitution  of  ether  as  established  by  its  synthesis 
from  sodium  ethylate  and  ethyl  iodide,  Williamson's  synthesis,  or 
from  ethyl  iodide  and  silver  oxide  (p.  106). 

Properties  of  Ether.  —  Ethyl  ether  is  the  common  ether  used  so 
generally  as  an  anesthetic  and  is  one  of  the  most  valuable  of  the  sub- 
stances made  from  alcohol.  In  its  manufacture  denatured  alcohol  is  an 
important  factor.  The  reason  why  the  denaturing  of  the  alcohol  by 
the  addition  of  sulphuric  acid  does  not  injure  the  alcohol  for  this  pur- 
pose is  apparent.  Ether  is  a  clear,  limpid  liquid  of  characteristic  odor 


ETHERS  III 

and  is  easily  volatile,  boiling  at  34.6°.  It  burns  and  is  very  inflammable 
because  it  is  so  volatile.  The  vapor  forms  an  explosive  mixture  with 
air,  and  it  is,  therefore,  extremely  dangerous  to  use  unless  great  pre- 
caution is  taken  to  guard  it  from  ignition.  It  does  not  dissolve  in 
water  except  in  small  amounts,  and  as  it  is  lighter  than  water,  specific 
gravity  0.736  (o°)  it  forms  a  non-miscible  layer  on  top  of  the  water 
whenever  the  two  are  mixed  and  then  allowed  to  stand  and  separate. 
This  property  is  made  use  of  very  often  in  separating  ether  and  water 
and  in  extracting  from  water  solution  substances  which  are  more  splu- 
ble  in  ether.  It  mixes  with  alcohol  in  all  proportions.  It  is  a  good 
solvent  for  many  organic  substances,  fats  and  alkaloids  especially. 
Because  of  its  rapid  evaporation  at  ordinary  temperatures  it  lowers  the 
temperature  of  a  body  sprayed  with  it. 


III.  OXIDATION  PRODUCTS  OF  ALCOHOLS 

H 

I 
(A)  ALDEHYDES       R— C=O 

Oxidation  of  Alcohol. — When  ethyl  alcohol  is  treated  with  potassium 
bichromate  in  the  presence  of  dilute  sulphuric  acid  a  volatile  substance 
with  a  peculiar  sweet  odor  is  given  off.  At  the  same  time  the  reduction 
of  the  bichromate  is  indicated  by  the  appearance  of  the  green  color 
characteristic  of  chromium  salts.  The  volatile  product  is  termed  an 
aldehyde,  specifically  acetaldehyde,  and  when  analyzed  proves  to  have 
the  composition,  C2H4O.  As  this  differs  from  the  alcohol  by  two  hydro- 
gen atoms  the  action  has  plainly  been  one  of  oxidation  by  which  two 
hydrogen  atoms  have  been  removed.  The  name  is  derived  from  this 
relation  to  alcohol,  from  the  two  words  al-(cohol)  dehyd-(rogenatum). 

Aldehydes  not  Hydroxy  Compounds. — The  question  arises,  which 
two  hydrogen  atoms  of  the  alcohol  have  been  removed  and  what  is  the 
constitution  of  the,  new  compound?  Alcohol  is  C2H5 — OH  or  CH3 — 
CH2 — OH  so  that  we  might  lose  two  hydrogen  atoms  in  various  ways. 
The  first  test  that  naturally  suggests  itself  is  to  determine  whether  the 
aldehyde  still  contains  the  hydroxyl  group  of  the  alcohol  or  is  this 
hydroxyl  hydrogen  one  of  those  removed?  When  treated  with  metallic 
sodium  acetaldehyde  forms  no  compound  nor  does  it  lose  one  hydrogen 
as  in  the  case  of  alcohol.  This  would  indicate  that  in  aldehydes  no 
one  atom  of  hydrogen  differs  from  the  others,  i.e.,  all  must  be  directly 
linked  to  carbon  and  no  hydroxyl  group  is  present.  In  proving  the  con- 
stitution of  alcohol  as  a  hydroxy  compound  (p.  80)  the  reaction  with 
phosphorus  tri-  and  penta-chlorides  established  it  as  analogous  to 
that  of  water.  The  reactions  are  as  follows: 

C2H6— OH  +  PC15       — >      C2H5— Cl  +  HC1  +  POC13 
3C2H5— OH  +  PC13    >    3C2H5— Cl         +        P(OH)3 

Ethyl  alcohol  Ethyl  chloride 

With  acetaldehyde  and  phosphorus  penta-chloride  the  products  of  the 
reaction  are  entirely  different.     There  is  no  formation  of  either  hydro- 

112 


ALDEHYDES 


chloric  acid  or  an  alkyl  chloride.  This  proves  that  in  aldehyde  there 
can  be  no  hydroxyl  group  as  the  formation  of  these  two  products, 
especially  the  hydrochloric  acid,  is  proof  of  the  existence  of  this  group. 
The  products  formed  are  phosphorus  oxy-chloride,  POC13,  and  a 
compound  which  by  analysis  proves  to  be  C2H4C12. 


C2H40 

Acetaldehyde 


PCL 


C2H4C12 

Di-chlor  ethane 


+         POC1; 


Plainly  the  reaction  here  is  the  same  as  that  given  as  the  probable  first 
step  in  the  action  of  phosphorus  penta-chloride  and  alcohol,  viz., 
two  atoms  of  chlorine  of  the  penta-chloride  have  been  exchanged  for 
oxygen  yielding  phosphorus  oxy-chloride,  POC13.  The  other  product 
in  the  aldehyde  reaction  has  been  shown  to  be  ethane  in  which  two 
hydrogen  atoms  are  substituted  by  two  chlorine  atoms,  i.e.,  a  di-chlor 
ethane.  Furthermore,  the  di-chlor  ethane  so  formed  is  the  unsymmetri- 
cal  compound  (p.  53),  in  which  two  hydrogen  atoms  linked  to  one 
carbon  have  been  substituted  by  two  chlorine  atoms.  It  must  be  then 
that  in  acetaldehyde  one  atom  of  oxygen  is  in  the  position  of  two  atoms 
of  hydrogen  linked  to  one  carbon  in  ethane.  These  relations,  between 
ethane,  unsymmetrical  di-chlor  ethane  and  acetaldehyde  may  be 
represented  as  follows: 


C2H6 
CH3— CH3 

H    H 

f      I 
H— C— C— H 


H    H 

Ethane 


C2H4C12 
CH3— CHC12 

H    H 

I       I 
H— C— C— Cl 


H    Cl 

Di-chlor  ethane 
(unsymmetrical) 


C2H4O 
CH3— CHO 

H    H 

I       I 
-  H— C— C  =O 

H 

Acetaldehyde 


Aldehydes,  then,  are  not  hydroxy  compounds  nor  are  they  oxides 
like  the  ethers.  In  them  the  oxygen  atom  is  linked  to  one  carbon  atom  by 
two  valencies  previously  satisfied  by  two  hydrogen  atoms  in  the  hydro- 
carbon mother  substance. 


114  ORGANIC  CHEMISTRY 

Carbonyl  Group. — This  group,  viz.,  =  C  =  O  is  known  as  car  bony  I 
and  it  is  present  in  other  compounds  also.  The  other  two  valencies  of 
the  carbon  to  which  the  oxygen  is  linked  are  satisfied  in  acetaldehyde, 
one  by  hydrogen,  the  other  by  methyl. 

Aldehyde  Group. — This  methyl  may  become  any  radical  thereby 
forming  an  homologous  series  of  aldehydes.  The  hydrogen,  however, 
remains  in  all  aldehydes  so  that  the  distinctive  aldehyde  formula  is 

H 

R— C  =  O    or    R— CHO 

It  will  be  well  to  note  that  in  writing  formulas  in  the  condensed  struc- 
tural form,  — COH  indicates  that  hydroxyl  is  linked  to  carbon  while 

( — CHO)  indicates  that  hydrogen  and  oxygen  are  linked  separately  to 
the  carbon. 

Alcohol  an  Oxidized  Hydrocarbon. — Our  first  statement  in  regard 
to  acetaldehyde  was  that  it  is  formed  by  oxidizing  alcohol.  This 
reaction,  and  the  further  oxidation  of  aldehydes  to  acids,  which  we  shall 
study  very  soon,  are  only  clear  when  we  consider  alcohols  as  the  first 
step  in  the  oxidation  of  hydrocarbons.  We  cannot  prepare  ethyl  alco- 
hol by  oxidizing  ethane,  and  we  have  shown  that  it  is  not  an  oxide, 
but  in  composition  it  is  plainly  an  oxidation  product,  i.e.,  ethane  plus 
oxygen.  We  can  consider  it  as  such  in  that  a  hydrogen  atom  of  ethane 
is  converted  into  hydroxyl  by  the  addition  of  oxygen,  the  oxygen  forming  the 
link  between  carbon  and  hydrogen.  We  may  represent  the  relationship 
as  follows: 

H    H  H    H 

H— C— C— H  +  0         -*      H— C— C— O— H 
H    H  H    H 

Ethane  Alcohol 

If  this  is  the  process  in  the  oxidation  of  compounds  containing  hydrogen 
linked  to  carbon  we  should  expect  a  second  oxygen  to  react  in  the  same 


ALDEHYDES  115 

way  and  a  di-hydroyl  compound  would  be  formed.  But  we  know  that 
when  alcohol  is  oxidized  we  obtain  an  aldehyde  which  we  have  shown 
has  the  constitution  previously  assigned  to  it.  On  examination  we  see 
that  this  formula  for  the  aldehyde  is  simply  the  anhydride  of  the  theo- 
retical oxidation  product  represented  as  an  intermediate  step  in  the 
oxidation  of  alcohol  to  acetaldehyde,  as  follows: 

H    H  H    H  H    H 

I  I       I  — HjO  |       | 

H— C— C— OH  +  O       — »    H— C— C— O(H       — >    H— C— C  =  O 

H    H  H  (OH)  H 

Alcohol  Di-hydroxy  compound  Acetaldehyde 

(theoretical) 

It  should  also  be  emphasized  that  when  oxidation  of  an  hydroxy  com- 
pound takes  place  the  carbon  group  that  is  oxidized  is  one  which  al- 
ready contains  hydroxyl.  This  formation  of  a  di-hydroxy  compound 
as  an  intermediate  product  in  the  oxidation  of  alcohol  to  an  aldehyde 
may  also  be  shown  to  be  the  probable  step  by  the  fact  that  acetalde- 
hyde may  be  made  from  unsymmetrical  di-brom  ethane  by  the  action 
of  water  as  follows : 

H    H  H    H 

|  — 2HBr          |       |  — H2O 

H— C— C— (Br  +  H)OH       ~»    H— C— C— O(H       — >" 

H  (Br          +  H)OH  H  (OH 

Unsymmetrical  Intermediate  product 

di-brom  ethane  (theoretical) 

H    H 

I      I 
H— C— C  =  O 

I 
H 

Acet-aldehyde 

Two  Hydroxyls  Linked  to  One  Carbon. — Now  a  great  many  cases 
have  led  to  the  conclusion  that  whenever  we  have  two  hydroxyls  linked 
to  one  carbon  an  unstable  grouping  is  the  result.  This  loses  water  as 
indicated  and  a  stable  anhydride  product  is  formed.  We  shall  find 


Il6  ORGANIC  CHEMISTRY 

later  that  when  two  hydroxyls  are  linked  to  two  different  carbons  a  stable 
compound  is  formed  which  does  not  lose  water. 

Addition  Products. — An  important  property  of  aldehydes  is  that 
they  readily  take  up  certain  compounds  and  form  addition  products. 
When  acetaldehyde  reacts  with  ammonia,  sodium  acid  sulphite  or 
hydrogen  cyanide  definite  crystalline  compounds  are  obtained.  The 
probable  reaction  is  that  the  double  union  between  carbon  and  oxygen 
is  broken  the  oxygen  being  converted  into  hydroxyl,  while  the  remainder 
of  the  added  compound  satisfies  the  other  valence  as  follows: 

H  H 

I  I 

CH3— C  =  O  +  H— NH2 >   CH3— C— OH  Acetaldehyde  ammo- 

Acetaldehyde  I 

nia 
NH2 

H  H 

I  ! 

CH3— C  =  O  +  H— SO8Na  -   -»  CH3— C— OH    Acetaldehyde 

sodium  acid  sulphite 
SO3Na 

H  H 

I  I 

CH3— C  =  O  +  H— CN  — *  CH3— C— OH    Acetaldehyde  hydrogen 

cyanide 

CN 

The  probability  that  these  are  the  formulas  for  the  addition  products 
is  based  upon  the  fact  that  the  formula  for  the  hydrogen  cyanide  com- 
pound is  fully  established  by  its  relationship  to  another  definite  com- 
pound, viz.,  lactic  acid,  on  account  of  which  it  is  known  as  lactic  acid 
nitrile.  This  will  be  explained  later  when  we  study  that  acid. 

Aldol  Condensation. — An  important  reaction  of  acetaldehyde,  which 
is  analogous  to  the  preceding  addition  reactions,  is  one  in  which  a  mole- 
cule of  acetaldehyde  forms  an  addition  product  with  itself,  the  two 
molecules  being  united  into  one.  The  reaction  is  designated  a  con- 


ALDEHYDES  1 17 

densation  and  from  the  name  of  the  product  it  is  termed  the  aldol 
condensation. 

H  H 

CH3— C   =  O  +  H)CH2— CHO    —- >     CH3— C— CH2— CHO 

Acetaldehyde 

OH 

Aldol 
2-Hydroxy  butanal-4 

Aldol  is  a  hydroxyl  substitution  product  of  normal  butyric  aldehyde 
or  butanal.  This  reaction  and  the  product  will  be  referred  to  later 
(p.  229). 

Acetal. — Under  certain  conditions,  by  passing  phosphine  gas, 
PH3,  into  a  mixture  of  alcohol  and  acetaldehyde,  the  two  compounds 
react  yielding  a  product  known  as  acetal. 

-H20 

CH3— CH(0  +  2H)0— C2H5 >         CH3— CH(OC2H5)2 

Acetaldehyde  Alcohol  Acetal 

Acetal  may  also  be  made  by  oxidizing  alcohol  when  the  above  reaction 
probably  takes  place.  It  is  present  too  in  crude  wood  distillate  from 
which  it  may  be  obtained. 

Polmyerization. — Another  property  of  aldehydes  that  should  be 
mentioned  is  that  some  of  them  readily  form  polymeric  compounds, 
i.e.,  compounds  of  the  same  percentage  composition,  but  some  multiple 
of  the  molecular  weight. 

C2H4O        >        (C2H4O)3  or  C6H12O3 

Acetaldehyde  Paraldehyde 

This  polymeric  aldehyde,  known  as  par-aldehyde,  is  a  definite  com- 
pound, but  it  does  not  react  like  an  aldehyde,  i.e.,  does  not  contain  the 
aldehyde  group.  The  polymerization  is  effected  by  simply  adding  a 
small  amount  of  acid.  Furthermore,  at  o°,  the  same  reaction  takes 
place,  but  a  distinctly  different  product  is  obtained  which  proves  to 
be  a  similar  polymeric  compound  of  the  same  formula  as  the  paralde- 
hyde.  This  is  known  as  met-aldehyde.  A  comparison  of  these  two 
compounds  shows  their  difference. 

Paraldehyde  Metaldehyde 

(C2H40)3  (C2H40)3 

Acetaldehyde  +  HC1  Acetaldehyde  +  HClato0 

Liquid,  B.P.  125°  Solid,  sublimes  at  112° 


Il8  ORGANIC  CHEMISTEY 

By  such  polymerization  then  two  isomeric  compounds  are  formed 
neither  of  which  contains  the  aldehyde  group. 

The  loss  of  aldehyde  properties  by  a  change  in  the  aldehyde  group  is 
due  to  the  union  of  the  three  molecules  into  a  ring.  The  isomerism  of 
the  two  polymers  is  probably  due  to  different  space  relations,  i.e., 
it  is  stereo-isonterism.  The  following  formula  has  been  suggested. 


CH3 


OHO  Paraldehyde 

and 
CH3—  C—  O—  C—  CH3        Metaldehyde 

H          H 

Reducing  Properties.  —  The  ease  with  which  aldehydes  are  oxidized 
makes  them  important  as  reducing  agents.  When  acetaldehyde  or 
the  ammonium  acetaldehyde  acts  upon  silver  nitrate  in  ammoniacal 
solution  the  silver  is  reduced  to  metallic  condition.  The  metallic 
silver  so  formed  is  in  an  exceeding  fine  condition  and  is  deposited  as 
a  brilliant  mirror  on  the  clean  surface  of  the  glass  vessel  in  which  the 
reaction  occurs. 

Nomenclature.  —  While  there  is  an  homologous  series  of  aldehydes 
as  of  the  other  compounds  we  have  studied,  only  a  few  of  them  are 
important.  The  official  names  correspond  exactly  to  those  for  the  al- 
cohols, the  termination  ol  of  alcohols  being  changed  to  al  for  the  alde- 
hydes. The  first  four  members  are  methanal,  ethanal,  propanal,buta- 
nal.  The  common  names  are  derived  from  the  fact  that  aldehydes 
on  further  oxidation  yield  acids,  the  name  of  the  acid  resulting  giving 
the  specific  name  to  the  aldehyde.  Formic  acid  is  obtained  from  formic 
aldehyde,  contracted  to  formaldehyde  ;  acetic  acid  from  acetic  aldehyde, 
acetaldehyde.  Those  two  aldehydes  are  the  most  common  and  the  only 
ones  we  shall  consider.  The  aldehydes  have  in  general  lower  boiling 
points  than  the  corresponding  alcohols  and  a  peculiar,  irritating  sweet 
odor.  Table  XIII  gives  the  names,  formulas  and  boiling  points  of  a 
few  aldehydes. 


ALDEHYDES 


IIQ 


TABLE  XIII. — ALDEHYDES  AND  KETONES 
Aldehydes 


Common  name 

Official  name 

Formula 

B.P. 

Methanal 

H  —  CHO 

—  21° 

Acetaldehyde 

Ethanal 

CHs  —  CHO 

20  8° 

Propanal 

CHs—  GHz—  CHO 

48  8° 

Butyric  aldehyde 

Butanal 

CHs—  CHr—  CHr-  CHO 

74   O° 

Iso-butyric  aldehyde 

2-Methyl  propanal. 

CHs—  CH—  CHO 

6l    0° 

Valeric  aldehyde 

Pentanal  

1 
CH8 
CHs—  CHr—  CHr—CHj  —  CHO 

103  4° 

Iso-  valeric  aldehyde 

2-Methyl  butanal-4  

CHs—  CH—  CHr—  CHO 

92.0° 

1 
CH3 

Ketones 


Acetone  (Di-methyl  ke- 

Propanone  

CHs—  CO  —  CHs 

565° 

Methyl  ethyl  ketone 

Butanone  

CHs—  CO—  CHr—  CH3 

80.6° 

Di-ethyl  ketone  
Methyl  propyl  ketone  
Methyl  iso-propyl  ketone.. 

Pentanone-3  
Pentanone-2  .  .  .  !  
2-Methyl  butanone-3-  .  .  . 

Undecanone-2 

CHs—  CHr—  CO—  CHr—  CHs 
CHs—  CH2—  CHr—  CO—  CHs 
CHs—  CH—  CO—  CHs 
1 
CHs 
CHs  —  CO  —  (CH2)  g  —  CHs 

102.0° 
102.7° 
95-0° 

224    O° 

M.P. 
+  15° 

Formaldehyde    H— CHO.    Methanal 

Formaldehyde  or  methanal  is  the  aldehyde  relate.d  to  methyl  al- 
cohol as  the  oxidation  product.  It  may  be  prepared  by  passing  a 
mixture  of  methyl  alcohol  vapor  and  air  over  hot  copper  or  platinum. 


H— CH2OH  +  O 

Methanol 


H— CHO  +  H2O 

Methanal 


The  reaction  continues  after  being  started  because  the  heat  of  the  re- 
action keeps  the  metal  hot.  It  is  a  gas,  b.p.  —21°,  and  is  readily 
soluble  in  water.  A  solution  containing  about  40  per  cent  is  the  com- 
mercial form  of  the  compound  known  as  formalin  sometimes  also  as 
formol.  Formaldehyde  is  a  valuable  preservative,  antiseptic  and 
germicide,  and  is  used  widely  in  disinfecting,  either  as  a  gas  or  in  the 
form  of  a  water  solution,  viz.,  as  formalin.  When  formalin  is  used  it 
is  sprinkled  upon  a  sheet  which  is  suspended  in  the  room,  the  formalde- 


120  ORGANIC  CHEMISTRY 

hyde  volatilizing  as  a  gas.  When  used  in  the  form  of  a  gas,  as  in  dis- 
infecting rooms  after  sickness,  it  is  freshly  generated  by  means  of  alcohol 
lamps  so  constructed  with  platinum  asbestos  that  the  reaction  above 
described  takes  place.  A  still  more  effective  way  is  by  the  action  of 
potassium  permanganate  upon  formalin.  When  formalin  is  poured 
upon  potassium  permanganate  a  vigorous  action  occurs  with  the  pro- 
duction of  much  heat  so  that  the  greater  part  of  the  formaldehyde  is 
volatilized.  The  action  is  quite  violent  and  the  gas  is  driven  rapidly 
throughout  the  entire  space  to  be  disinfected. 

Acetaldehyde    CHs— CHO.    Ethanal 

Acetaldehyde  or  ethanal  is  the  second  member  of  the  series  and 
corresponds  to  ethyl  alcohol  from  which  it  is  made  by  oxidizing  with 
chromic  acid  (potassium  bichromate*  and  sulphuric  acid). 

CH3— CH2OH  +  O        >        CH3— CHO  +  H2O 

Ethanol  Ethanal 

The  name  ethanal  indicates  its  relation  to  ethyl  alcohol  while,  as  it 
forms  acetic  acid  on  further  oxidation,  it  is  known  also  as  acetaldehyde. 
It  is  a  volatile  liquid  boiling  at  20.8°,  and  possessing  a  sharp  sweet  odor. 
It  is  soluble  in  water,  alcohol,  and  ether. 

R 

i 
(B)  KETONES    R— C  =  O 

Ketones  are  also  oxidation  products  of  alcohols.  We  should  re- 
call that  there  are  three  different  kinds  of  alcohols  isomeric  because  of 
the  different  places  in  the  hydrocarbon  chain  in  which  the  hydroxyl  is 
substituted.  These  alcohols  we  have  called  primary,  secondary  and 
tertiary,  and  each  one  contains  a  characteristic  group,  viz., 

R  R 

I  I 

R— CH2OH  R— CH— OH  R— C— OH 

Primary  alcohols  Secondary  alcohols 

R 

Tertiary  alcohols 


KETONES  121 

Primary  Alcohols  Yield  Aldehydes. — Now  methyl  alcohol  and  ethyl 
alcohol  which  yield  the  two  aldehydes  that  have  been  studied  are  both 
of  them  primary  alcohols,  and  it  has  been  found  to  be  true  that  only 
primary  alcohols  yield  aldehydes  on  oxidation.  Normal  propyl  alcohol, 
propanol-i,  and  other  primary  alcohols  thus  yield  aldehydes. 

CH3— CH2— CH2OH  +  O  — >        CH3— CH2— CHO 

Propanol-i  Propanal 

Secondary  Alcohols  Yield  Ketones. — The  isomeric  propyl  alcohol, 
viz.,  the  secondary  alcohol,  propanol-2,  on  oxidation  yields  a  com- 
pound the  composition  of  which  is  C3HeO,  but  which  is  not  an  aldehyde. 
It  is  known  as  a  ketone,  specifically  as  acetone,  and  is  isomeric  with 
propanal  the  aldehyde  obtained  from  normal  propyl  alcohol. 

CH3— CH(OH)— CH3  +  O        >        C3H60  +  H2O 

Propanol-2  Acetone 

As  only  those  alcohols  which  are  primary  yield  aldehydes  so  also  only 
those  which  are  secondary  yield  ketones.  The  relation  in  composition 
between  the  secondary  propyl  alcohol  and  acetone  is  the  same  as 
between  ethyl  alcohol  and  acetaldehyde.  What  then  is  the  con- 
stitution of  ketones  and  why  do  secondary  alcohols  not  oxidize  to 
aldehydes  but  to  ketones? 

Action  of  PC15  on  Ketones. — When  phosphorus  penta-chloride 
reacts  with  acetone  it  acts  just  as  it  does  with  aldehydes,^., it  removes 
oxygen  and  substitutes  two  chlorine  atoms  in  its  place.  The  product 
is  2-2-di-chlor  propane. 

C3H60  +  PC15 >        C3H6C12  +  POC13 

CH3— CO— CH3      PC15  — >        CH3— CC12— CH3      POC13 

Acetone  2-2-Di-chlor  propane 

Carbonyl  Group  in  Ketones. — This  reaction  would  indicate  the 
presence  of  the  carbonyl  group,  (=  CO),  and  the  structure  as  written. 
Now  acetone  by  reduction  yields  propanol-2  and  conversely  is  formed 
from  it  by  oxidation.  Propanol-2  is  CH3 — CH(OH) — CH3,  i.e.,  there 
are  two  methyl  groups  present.  Do  these  two  methyl  groups,  however, 
remain  in  acetone  as  they  exist  in  the  alcohol?  We  have  stated  pre- 
viously (p.  115)  that  the  oxidation  of  primary  alcohols  probably  takes 


122  ORGANIC  CHEMISTRY 

place  by  the  conversion  of  a  hydrogen  into  a  second  hydroxyl  group 
and  that  this  product  loses  water  and  gives  us  aldehyde  as  follows: 

H    H    H  H    H    H 

111                   +0  111  -H-OH 

H— G— C— C— OH >        H— C— C— C— 0(H)  -> 

111  111 

H    H    H  H    H  (OH) 

Propanol-i  Intermediate  compound 

(Primary  alcohol) 

H    H    H 

I       1       I 
H— C— C— C  =  O 

I      I 
H    H 

Propanal 

(Aldehyde) 

Structure  of  Ketones. — If  propanol-2  is  oxidized  in  the  same  way  we 
should  obtain  an  intermediate  product  containing  two  hydroxyl  groups 
linked  to  one  carbon  atom  and  this  would  lose  a  molecule  of  water  as 
follows : 

H  (OH) 

|  |  -H— OH 

CH3— C— CH3  +  0  >    CH3— C— CH3     >     CH3— C— CH3 

I  I  II 

OH  O(H)  O 

Propanol-2  Intermediate  Acetone 

compound 

The  conclusive  proof  that  in  acetone  there  are  two  methyl  groups  pres- 
ent is  in  the  synthesis  of  acetone  from  acetic  acid  and  acetyl  chloride, 
reactions  which  we  shall  soon  study.  With  this  conclusive  proof  our 
formula,  as  we  have  written  it,  must  be  correct  and  our  ideas  in  regard 
to  the  oxidation  of  compounds  containing  hydrogen  linked  to  carbon 
are  probably  correct  also.  The  steps  in  the  oxidation  are  probably 
as  we  have  indicated,  viz.,  that  hydrogen  is  first  converted  into  hydroxyl 
and  when  as  a  result  of  such  oxidation,  two  hydroxyls  are  linked  to  one 
carbon,  the  compound  loses  water,  leaving  one  oxygen  doubly  linked  to  the 
carbon.  This  enables  us  to  understand  the  facts  that  only  primary 
alcohols  on  oxidation  yield  aldehydes,  secondary  alcohols  yield  ketones, 
while  tertiary  alcohols  yield  neither  aldehydes  nor  ketones. 

Oxidation  of  Primary  Alcohols. — In  the  primary  alcohol  group, 
( — CH2OH),  there  are  two  unoxidized  hydrogens. 


KETONES  123 

By  the  oxidation  of  one  to  hydroxyl  and  the  loss  of  water,  leaving 
a  doubly  linked  oxygen,  there  will  still  be  one  unchanged  hydrogen 
united  to  the  carbon  so  that  the  group  — CH2OH  becomes  — CHO, 
i.e.,  the  aldehyde  group. 

Oxidation  of  Secondary  Alcohols. — In  the  secondary  alcohol  group 
( — CHOH — )  there  is  only  one  hydrogen  in  addition  to  the  hydroxyl 
group  so  that  on  its  conversion  into  hydroxyl  and  the  subsequent  loss 
of  water  there  is  left  no  hydrogen  united  to  this  carbon,  and  we  obtain 

the  ketone  group,  • — C  =  O. 

Oxidation  of  Tertiary  Alcohols. — In  the  case  of  tertiary  alcohols  it 
is  a  fact  that  on  oxidation  they  yield  neither  aldehydes  nor  ketones. 
This  agrees  with  our  ideas  as  there  is  no  hydrogen  linked  to  the  carbon 
which  has  the  hydroxyl.  Oxidation,  therefore,  does  not  take  place 
readily  nor  without  breaking  the  carbon  chain. 

Distinguishing  Reactions  of  the  Three  Classes  of  Alcohols. — This 
distinction  between  primary,  secondary  and  tertiary  alcohols  is  of 
fundamental  importance  and  is  the  characteristic  difference  that  is 
used  to  tell  whether  an  alcohol  belongs  to  one  class  or  another.  To  put 
it  all  together 

H  H 

I  I 

Primary  alcohols  R— C— OH  +  O  — »        Aldehydes  R— C  =  O 

H 

R  R 

I  I 

Secondary  alcohols   R— C— OH  +  O     >     Ketones,  R— C  =  O 

H 
R 

Tertiary  alcohols      R— C— OH  +  O       — »    Do  not  yield  either  alde- 
hydes or  ketones,  but 
R  break  down. 

Comparison  of  Aldehydes  and  Ketones. — The  difference  between 
aldehydes  and  ketones  in  their  structure  is  simply  that  in  ketones  the 


124  ORGANIC  CHEMISTRY 

bivalent  carbonyl  group  is  linked  to  two  radicals  while  in  aldehydes  it  is 
linked  to  one  radical  and  to  one  hydrogen.  The  characteristic  reactions 
of  aldehydes  depending  upon  the  carbonyl  group  we  would  thus 
expect  to  take  place  with  ketones  also.  This  is  true,  for  ketones, 
like  aldehydes,  form  addition  products  with  hydrogen  cyanide  and 
sodium  acid  sulphite.  With  ammonia,  however,  they  do  not  form 
simple  addition  products  but  lose  water  so  that  the  resulting  compounds 
are  not  of  the  same  character  as  aldehyde  ammonia.  Likewise  the 
reactions  of  the  aldehydes,  which  depend  upon  the  presence  of  the 
hydrogen  linked  to  the  carbonyl  carbon  group,  we  should  not  expect 
to  occur  with  the  ketones.  This  is  true  in  the  case  of  their  oxidation 
as  they  yield  entirely  different  products.  It  is  also  true  in  regard  to 
transformation  into  polymeric  forms  which  does  not  take  place  with 
ketones.  This  would  indicate  that  the  polymerization  of  aldehydes 
is  in  some  way  associated  with  the  presence  of  hydrogen  linked  to  the 
carbonyl  carbon.  As  ketones  do  not  oxidize  readily  they  differ  from 
the  aldehydes  in  not  being  good  reducing  agents. 

Names  of  Ketones.— The  systematic  names  of  the  ketones  differ  from 
those  of  the  alcohols  and  aldehydes  only  in  the  termination  one  which 
is  added  to  the  name  of  the  hydrocarbon.  The  position  of  the  carbonyl 
is  denoted  as  in  other  cases  by  the  number  following. 

Acetone    Propanone    Di-methyl  Ketone 
CH-r-  CO— CH3 

The  only  ketone  which  we  shall  consider  is  acetone,  CH3 — CO — 
CH3,  or  propanone,  also  called  di-methyl  ketone.  Acetone  is  a  liquid 
that  boils  at  56.5°.  It  has  a  peculiar  odor,  and  is  soluble  in  all  propor- 
tions in  water.  It  is  a  valuable  solvent  for  many  organic  substances, 
and  is  used  in  the  manufacture  of  explosives  and  in  important  syn- 
thetic reactions.  It  is  the  third  important  constituent  of  crude  wood 
alcohol  or  pyroligneous  acid,  being  formed  as  a  product  of  the  dry 
distillation  of  wood.  Table  XIII  gives  the  names,  formulas  and  boil- 
ing points  of  a  few  of  the  more  common  and  important  ketones. 

DERIVATIVES  OF  ALDEHYDES  AND  KETONES 

Oximes  and  Hydrazones 

R  R 

I  I 

R— C  =  N— OH  R— C  =  N— NH— C6H5 


OXIMES    AND    HYDRAZONES  1 25 

Two  classes  of  compounds  should  be  mentioned  at  this  time  as  they 
are  derivatives  of  both  aldehydes  and  ketones.  We  have  spoken  of 
the  two  compounds  hydroxyl  amine,  NH2(OH)  and  phenylhydrazine, 
C6H5 — NH — NH2  (p.  63).  With  compounds  containing  the  car- 
bonyl  group  these  react  in  a  similar  way.  The  oxygen  of  the  carbonyl 
unites  with  the  two  hydrogens  of  the  primary  amine  group  forming  water, 
the  two  residues  uniting  to  form  a  new  compound. 

H  H 

I  I        ' 

CH3— C     =     (O  +  H2)N— OH       -4    CH3— C  =  N-OH  +  H2O 

Acetaldehyde  Hydroxyl  amine  Acet-aldoxime 

CH3  CH3 

CH3— C  =  (O  +  H2)N— OH    >     CH3— C  =  N— OH  +  H2O 

Acetone  Acet-ketoxime 

The  compounds  formed  with  hydroxylamine  are  known  as  oximes 
those  from  aldehydes  are  called  ald-oximes  and  those  from  ketones 
ket-oximes.  The  compounds  resulting  from  the  action  of  phenylhydra- 
zine  on  aldehydes  or  ketones  are  known  as  hydrazones. 

H  H 

I  I 

R— C  =  (O  +  H2)N— NH— C6H5 >  R— C  =  N— NH— C6H6  +  H2O 

Aldehyde  Phenyl  hydrazine 

R  R 

I  I 

R— C  =  (0  +  H2)N— NH— C6H5 >  R— C  =  N— NH— C6H5  +  H2O 

Ketone  Hydrazones 

These  two  reactions  are  characteristic  of  the  carbonyl  group  and  are 
used  in  determining  its  presence  in  compounds.  They  have  been  of 
especial  importance  in  the  study  of  the  sugars. 

(C)  ACIDS  R— COOH 

Relation  to  Alcohols. — The  third  class  of  oxidation  products  of  the 
alcohols  consists  of  the  acids.  Strictly  speaking  they  should  be  called 
oxidation  products  of  aldehydes,  but  as  the  latter  are  formed  directly 
from  the  alcohols  the  acids  are  generally  included  in  the  group  of  alco- 
hol oxidation  products. 


126  ORGANIC  CHEMISTRY 

Composition  and  Constitution. — We  have  already  spoken  of  the 
fact  that  the  aldehydes  are  named  from  the  acids  to  which  they  are  re- 
lated. When  formaldehyde  is  oxidized  it  yields  formic  acid  which  has 
the  composition  CH2O2  and  acetaldehyde  yields  acetic  acid,  C2H4O2. 
Each  acid  contains  one  atom  of  oxygen  more  than  the  aldehyde.  The 
relation  in  composition  between  hydrocarbons,  alcohols,  aldehydes 
and  acids  is 

Hydrocarbon  Alcohol  Aldehyde  Acid 

CH4  CH4O  CH2O  CH2O2 

Methane  Methyl  alcohol  Formaldehyde  Formic  acid 

Methanol  Methanal  Methanoic  acid 

C2H6  C2H6O  C2H4O  C2H4O2 

Ethane  Ethyl  alcohol  Acetaldehyde  Acetic  acid 

Ethanol  Ethanal  Ethanoic  acid 

What  is  the  constitution  of  the  acids  and  does  it  explain  them  as 
oxidation  products  of  alcohols  and  aldehydes? 

Action  of  Metals. — The  action  of  metals  on  acids  shows,  in  case  they 
are  mono-basic,  that  in  them  one  hydrogen  atom  is  different  from  the 
others  as  it  is  replaceable  by  metals  with  the  formation  of  salts. 

Action  of  PC15. — The  action  of  phosphorus  pentachloride  proves 
that  acids  contain  a  hydroxyl  group  as  products  are  formed  exactly 
analogous  to  those  obtained  from  alcohol  (p.  81).  The  products  are 
hydrochloric  acid,  phosphorus  oxychloride  and  a  derivative  of  the  acid 
which  contains  one  chlorine  atom  in  place  of  one  oxygen  and  one  hydro- 
gen as  hydroxyl. 

In  these  reactions  of  acetic  acid  with  phosphorus  pentachloride 
and  with  metals,  only  one  oxygen  anol  one  hydrogen  are  involved  show- 
ing that  the  other  oxygen  and  three  of  the  hydrogens  are  different. 
From  this  we  can  conclude  at  least  that  the  formula  for  acetic  acid, 
C2H4O2,  may  be  written  C2H3O(OH).  Are  the  three  remaining  hydro- 
gen atoms  linked  to  one  carbon  as  methyl,  ( — CH3)?  The  synthesis 
of  acetic  acid  by  the  oxidation  of  ethyl  alcohol  which  contains  the 
methyl  group  would  indicate  that  this  is  so.  We  have,  however, 
better  evidence  than  this. 

Presence  of  Methyl. — Methyl  cyanide,  which  is  the  cyanide  sub- 
stitution product  of  methane,  CH3 — CN,  yields  acetic  acid  when  boiled 
with  water.  The  methyl  group  must,  therefore,  undoubtedly  be  present 
in  acetic  acid.  This  would  further  make  it  probable  that  the  other 


SATURATED   MONOBASIC   ACIDS  127 

oxygen  and  other  carbon  are  linked  as  carbonyl  and  the  complete  struc- 
tural formula  would  be, 

H 

H—  C—  C—  OH        Acetic  acid        CH3—  CO—  OH 

I      II 
H    O 

The  group  (  —  COOH)  is  known  as  the  carboxyl  group.  The  general 
formula  for  acids  of  this  class  is  then  R—  COOH  or  (CnH2n+i)—  COOH 
which  agrees  with  our  conception  of  the  valence  of  carbon.  The  re- 
action between  acetic  acid  and  phosphorus  pentachloride  and  that 
between  the  acid  and  sodium  may  then  be  written  as  follows: 

CH3—  CO—  OH  +  PC15    -  >    CH3—  CO—  Cl  +  POC13  +  HC1 

Acetic  acid  Acetyl  chloride 

CH3—  CO—  OH-f-Na    -  >    CH3—  CO—  ONa  +  H 

Sodium  acetate 

The  synthesis  of  acetic  acid  from  methyl  cyanide  or  acetic  nitrile  by 
the  action  of  water  may  also  be  written  now  as  follows: 


CH3—  C(N  H-  -  >  CH3—  C—  OH  +  NH3  -  > 

Methyl  cyanide         *12JU  II 

Acetic  nitrile 

O 

Acetic  acid  CH3—  CO—  ONH4 

Ammonium  acetate 

Oxidation  Reactions.  —  This  constitution  of  acids  is  in  accord  with 
the  process  of  the  oxidation  of  hydrogen  linked  to  carbon,  as  was  dis- 
cussed under  aldehydes  and  ketones.  The  remaining  hydrogen  of  the 
aldehyde  group  is  converted  into  hydroxyl  and  we  may  represent  the 
entire  oxidation  from  hydrocarbon  to  acid  as  follows: 

H    H  H    H 

|       |  +0  +0 

H—  C—  C—  H    -  >    H—  C—  C—  OH    -  > 

I  I 

H    H  H   H 

Hydrocarbon  Alcohol 

Ethane  Ethyl  Alcohol 


128 


ORGANIC  CHEMISTRY 

H    H 

I  I 

H— C— C— 0(H 

H    (OH 
-H2O 

H    H 

I       I  + 

H— C— C=O 

H 

Aldehyde 


+  0 


0 


Acet 


dehyde 
-aldehyde 


H— C— C  =  O 


H 

Acid 
Acetic  acid 


The  strong  indication  even  though  it  may  not  be  proof  that  this  is  the 
mechanism  of  the  oxidation  process,  is  furnished  by  the  fact  that  we 
know  esters  of  the  normal  acid  containing  the  three  OH  groups.  These 
esters  by  hydrolysis  yield  the  acid. 


OR 
CH3— C— OR  +  3H— OH 


OR 

Ester  of  normal 
acetic  acid 


(OH) 

-H20 
CH3— C— OH  >   CH3— C— OH 


0(H 

Normal  acetic 
acid 

(theoretical) 


O 

Acetic  acid 


It  is  a  fact  also,  as  previously  stated,  that  ketones  do  not  yield  acids  on 
oxidation  without  breaking  down  and  this  is  readily  understood  as  there 
is  no  hydrogen  remaining  which  is  linked  to  the  carbonyl  carbon  and 
thus  possible  of  being  converted  into  hydroxyl,  e.g.,  in  acetone,  CH3 — 
CO— CH3. 

Stability  of  Carbon  Hydrogen  Groups. — In  our  early  discussion  of 
the  paraffin  hydrocarbons  we  spoke  of  the  fact  that  their  stability  is  a 
characteristic  property  as  illustrated  by  their  inactivity  toward  ordinary 
reagents,  (e.  g.)  in  oxidation  reactions.  This  general  stability  of  groups 
composed  of  carbon  and  hydrogen  is  strikingly  confirmed  by  the  relation 
of  substitution  products  of  the  hydrocarbons  toward  oxidizing  agents. 
The  substituted  hydrocarbons  are  always  more  easily  oxidized  than 
the  hydrocarbons  themselves  and  in  such  oxidation  it  is  always  the 


SATURATED    MONOBASIC   ACIDS 


I29 


carbon  group  in  which  previous  substitution  has  taken  place  that  is 
attacked  by  the  oxygen.  When  there  remains  in  this  group  one  or 
more  hydrogen  atoms  linked  to  carbon  the  oxidation  always  converts 
one  of  these  hydrogens  into  hydro xyl.  If  no  hydrogen  is  left  oxida- 
tion takes  place  with  much  more  difficulty,  and  then  only  by  the 
breaking  apart  of  the  carbon  chain. 

Before  we  proceed  with  the  homologous  series  of  acids  and  the  dis- 
cussion of  the  individual  members  it  may  be  well  to  gather  together  in 
one  outline  the  relationships  in  constitution  which  have  been  estab- 
lished between  all  of  the  classes  of  compounds  thus  far  considered. 


H 


H 


H 


.     R— C— O— C— R    R— C— O— OC— R 


H 

R— C— H- 

I 
H 

Hydrocarbon 


H          H 

Ether 


H 

Alkyl  halide, 
Primary 


H 

Ester  or  Ethereal 
salt 

H 


\ 


\ 


H                    H                        H  OH 

I                                 +0         |         +0         | 
>R— C— I »R— C— OH »R— C  =  O >R— C  =  O 

I  I  Aldehyde  Acid 


H 

Primary 
alcohol 


R                      R  R                        R 

I                       I  I            +0        |         +0 

R— C— H >R— C— I >R— C— OH >R— C  =  O >Breaks 

|                        |  |                      Ketone                       down 

H                     H  H 

Hydrocarbon            Alkyl  halide,  Secondary 

Secondary  alcohol 


R  R  R 

I                       I                                 +0 
R— C— H »R— C— I »R—  C— OH >Breaks  down 


R 

Hydrocarbon 


R 

Alkyl  halide, 
Tertiary 


R 

Tertiary 
alcohol 


130  ORGANIC  CHEMISTRY 

Homologous  Series. — The  two  acids,  formic  and  acetic,  are  the  first 
two  members  of  an  homologous  series  corresponding  to  the  similar 
series  of  hydrocarbons  and  alcohols. 

Hydrocarbon  Alcohol  Acid 

H— CH3  H— CH2OH  H— COOH 

Methane  Methyl  alcohol  Formic  acid 

Methan-ol  Methanoic  acid 

CH3— CH3  CH3— CH2OH  CH3— COOH 

Ethane  Ethyl  alcohol  Acetic  acid 

Ethan-ol  Ethanoic  acid 

In  formic  acid  the  simplest  member  of  the  series  the  radical  of  the 
general  formula  R — COOH  becomes  simply  H.  The  rest  of  the  series 
may  be  illustrated  by  the  more  important  members  given  in  the  follow- 
ing table. 

Names  of  Acids. — The  common  names  of  the  normal  acids  are  de- 
rived from  words  having  some  relation  to  their  occurrence  or  properties, 
e.g.,  butyric,  from  butter,  valeric  from  Valeriana,  etc.  The  official 
names  are  derived  by  adding  the  termination  oic  to  the  root  of  the  name 
for  the  hydrocarbon  of  the  same  number  of  carbon  atoms.  This  will 
be  understood  by  examining  the  names  given  in  the  table  and  comparing 
with  the  formulas. 

Isomerism. — Isomerism  in  the  case  of  the  acids  is  of  the  same 
character  as  that  of  the  alkyl  halides  and  the  alcohols  if  we  consider 
the  acids  as  mono-carboxyl  substitution  products  of  the  hydrocarbons. 
In  the  five  carbon  acids,  the  pentanoic  or  valeric  acids,  we  have  one 
compound  which  possesses  an  asymmetric  carbon  atom.  It  is  the  2- 
methyl  butanoic-i  acid.  According  to  the  van't  Hoff-LeBel  theory  this 
compound  should  exist  in  three  forms,  dextro,  lew  and  inactive.  By  oxi- 
dation of  the  fermentation  amyl  alcohol  which  is  a  mixture  of  2 -methyl 
butanol-i  and  2-m ethyl  butanol-4  there  is  obtained  a  mixture  of  two 
of  the  valeric  acids,  viz.,  the  2-methyl  butanoic-i  acid  and  the  2- 
methyl  butanoic-4.  This  same  mixture  is  found  naturally  in  the  roots 
of  Valeriana  officinalis.  By  separating  out  the  2-methyl  butanoic-4 
acid  the  2-methyl  butanoic-i  acid  is  obtained.  This  acid  is  inactive, 
but  has  never,  with  certainty,  been  separated  into  its  optical  compo- 
nents, though  it  is  claimed  that  a  dextro  form  has  been  obtained. 

Methods  of  Preparation. — The  general  methods  of  preparing  the 
acids  are  the  following:  (i)  From  the  acid  nitriles  by  boiling  with  water. 
In  this  reaction  the  carbon  of  the  cyanogen  radical  of  the  nitrile  re- 


SATURATED   MONOBASIC   ACIDS 


PQ 

°o       V 

- 

c  10   <>  in  in 

w    O    O    N    fO 
O    M    ^-  O    V) 

o   m 

0    O 

88 

o  o  o 

Tj-  \O     O 

j|   0    00     0     N     0 

Formula 

H—  COOH 
CHa—  COOH 
CHa—  GHz—  COOH 
CHa—  GHz—  GHz—  COOH 
CHa—  CH—  COOH 

CHa 

CHa—  CH_—  CHz—  CHz—  COOH 
CHa—  CH—  CHz—  COOH 

CHa 
CHa—  GHz—  CH—  COOH 

1 
CHa 

CHa 
I 
CHa—  C—  COOH 

1 
r~a. 

CHa—  GHz—  CHz—  CH»—  CHz—  COOH 
CHa—  CH—  CH,—  CHz—  COOH 
1 

HOOD—  •  (ZHD) 

HOOD—  «(«HO) 
HOOD—9  OHO) 
*HO 

(GHz)  10—  COOH 
(GHz)  it—  COOH 
(GHz  H—  COOH 
CCHz)  i«i—  COOH 
(CHz)  is—  COOH 

O  O  O 

a  a  aaa 
o  o  o  o  o 

Common  name  ^  Official  name 

Methanoic  
Ethanoic  
Propanoic  
Butanoic  .  .  .  
2-Methyl  propanoic  

Pentanoic  
2-Methyl  butanoic-4  

2-Methyl  butanoic-i  

2-2-Di-methyl  propanoic  

1  ; 

Hexanoic  
2-Methyl  pentanoic-S  

•      ; 

: 

:      : 

:          :  ' 

Heptanoic  
Octanoic  
Decanoic  

Dodecanoic  
Tetradecanoic  ...  
Hexadecanoic  
Octadecanoic  
Eicosanoic  

to 

O 

o 

1 

1 

0) 

1 

• 

10 

O 
o 

g 

** 

666 

2   2   2   2   g 
O  O  O  O  o 

O  O  O  O  O 

O  O 

• 

" 

Caproic  
Iso-caproic  

nlti 

Valeric  
Iso-valeric.  .  .  . 

o 

:          :   : 

Hi 

o<3<3 

lllll 

132  ORGANIC  CHEMISTRY 

mains  linked  to  the  carbon  of  the  alkyl  radical.  The  nitrogen  of  the 
cyanogen  radical,  however,  breaks  away  and  with  three  hydrogen 
atoms  from  two  molecules  of  water  it  forms  ammonia.  From  the 
water  there  remains  one  oxygen  and  hydroxyl,  (OOH),  which  with  the 
cyanogen  carbon  forms  carboxyl,  (COOH).  This,  it  will  be  recalled, 
is  the  proof  that  in  the  nitrile,  or  cyanide,  carbon  is  linked  to  carbon 
(p.  68).  The  reaction  is  very  clear  if  written  as  follows: 

H)OH 

H)                                              /H 
R— C(N  +       )O  -  — >  R— C— OH  +  N^H  >  R— CO— ONH4 

ixyf  \TT  Ammonium  Salt 

Acid  nitrile  ^  Ammonia 

Acid 

(2)  From  sodium  alkyls  and  carbon  dioxide.     In  this  reaction  the 
carbon   dioxide   seems   to   enter   the   compound  directly  forming  the 
carboxyl  group. 

R— Na    +    CO2        >        R— COONa 

Sodium  alkyl  Sodium  salt  of  the  acid 

(3)  From  sodium  alcoholates  and  carbon  monoxide.     This  is  analo- 
gous to  the  above,  the  carboxyl  group  being  formed  by  the  direct 
entrance  of  the  carbon  monoxide. 

R— ONa  +  CO      >      R— COONa 

Alcoholate  Sodium  salt  of  the  acid 

(4)  In  the  case  of  formic  acid  this  last  synthesis  is  from  sodium 
hydroxide  and  carbon  monoxide  and  is  the  commercial  method  of 
making  this  acid. 

H— ONa   +    CO >        H— COONa 

Sodium  hydroxide  Sodium  formate 

(5)  From  alcohols  or  aldehydes  by  oxidation  as  previously  discussed. 

R— CH2OH    >    R— CHO >    R— COOH 

Alcohol  Aldehyde  Acid 

These  are  the  general  methods  which  do  not  involve  other  compounds 
than  those  we  have  already  studied. 

Properties. — The  general  relation  in  physical  properties  between 
the  members  .of  the  homologous  series  of  acids  is  like  that  in  the  ho- 
mologous series  of  hydrocarbons  and  alcohols.  The  lower  members 
are  liquids  while  the  higher  members  are  wax-like  solids. 


SATURATED    MONOBASIC   ACIDS  133 

Reactions.  —  The  acid  properties  of  these  compounds  and  their 
ability  to  form  salts  is,  of  course,  their  most  prominent  reaction. 
Several  other;  reactions,  in  particular  those  with  alcohols  and  phos- 
phorus pentachloride,  will  be  discussed  under  the  subject  of  deriva- 
tives of  the  acids. 

Hydrocarbons  from  Acids.  —  One  reaction  to  be  spoken  of  at  this 
time  is  the  transformation  of  the  acids  into  hydrocarbons.  This  has 
already  been  referred  to  as  the  simplest  method  of  preparing  methane 
(p.  7).  When  an  organic  acid  loses  carbon  dioxide  it  is  converted 
into  a  hydrocarbon  with  one  less  carbon  atom  than  the  acid  itself. 

-  CO2  -  CO2 

CH3—  COOH       -»     CH3—  H    or    R—  COOH       —  >    R—  H 

Acetic  acid  Methane  Any  acid  Hydro- 

Ethanoic  acid  carbon 

This  is  a  general  reaction  for  preparing  hydrocarbons  and  is  the  reverse 
of  the  second  general  method  of  preparing  acids  as  given  above.  It 
is  usually  accomplished  by  heating  the  acid  with  an  alkali,  e.g.,  sodium 
or  calcium  hydroxides. 

Ketones  from  Acids.  —  Another  important  reaction  of  acids  is  the 
formation  of  ketones  and  aldehydes  by  the  decomposition  of  salts  of  the 
acids.  When  calcium  acetate  is  heated  the  calcium  remains  combined 
with  part  of  the  two  carboxyl  groups  as  calcium  carbonate  and  the 
two  alkyl  radicals  become  united  by  the  remaining  carbonyl  group  form- 
ing a  ketone. 

CH3 
CH3—  (COO,  | 

Va)        —  >     CH3—  CO     +     CaCO3 

CH3  —  CO(O  Propanone 

Calcium  acetate 

If  a  mixture  of  the  calcium  salts  of  a  higher  acid  and  of  formic  acid  is 
heated  an  aldehyde  results. 

H  —  (CO-0—  Ca)—  (O  —  OC)—  H  calcium  formate 

-2CaCO3 


CO-(0)-(Ca-0)-OC—  CH,  Calcium  acetate 

H  H 


CH3—  C  =  O  +         O  =  C—  CH3 

Acetalde 


134  ORGANIC  CHEMISTRY 

These  are  general  methods  for  the  formation  of  ketones  and  aldehydes. 
By  the  first  action,  if  the  salt  of  only  one  acid  is  used,  the  ketone  will 
always  be  a  simple  ketone  and  will  contain  the  same  alkyl  radicals  as 
the  acid.  In  case  a  mixture  of  acids  other  than  formic  acid  is  used  the 
product  will  be  partly  a  mixed  ketone  containing  the  two  alkyl  radicals 
of  the  acids  used.  The  second  reaction  always  yields  the  aldehyde 
corresponding  to  the  acid  other  than  formic. 

Occurrence. — The  members  of  this  series  of  acids  are  derived  from 
the  methane  series  of  hydrocarbons  and  occur  very  commonly  in  nature. 
In  a  few  cases  they  are  found  free  as  formic  acid  in  ants  and  nettles 
and  valeric  acid  in  the  root  of  Valeriana.  In  most  cases  the  acids  are 
combined  with  alcohols  as  esters  and  as  such  are  found  in  ethereal  oils, 
fats  and  waxes.  This  has  given  them  the  name  fatty  acids. 

Formic  Acid    H— COOH    Methanoic  Acid 

Formic  acid,  the  simplest  of  the  fatty  acids,  is  found  free  in  nature 
as  just  stated,  the  name  for  ants,  viz.,  Formici-dce,  giving  the  name  to 
the  acid.  It  is  a  liquid,  B.  P.  101°  with  a  very  sharp  odor  and  an 
irritating  or  blistering  effect  upon  the  skin.  It  yields  well  crystallized 
salts  of  the  metals  especially  of  copper,  lead  and  calcium.  It  may  be 
prepared  by  the  general  methods  given  above,  e.g.: 

H— CN         +         2H2O    — ->    H— COOH     +     NH3 

Hydrogen  Formic  acid 

Formic  nitrile 

H— ONa       +        CO          >    H— COONa 

Sodium  hydroxide  Sodium  formate 

H— CHO      +         O          >    H— COOH 

Formaldehyde  Formic  acid 

The  commercial  method  of  making  formic  acid  is  by  the  second  reac- 
tion. It  is  of  especial  importance  in  the  manufacture  of  oxalic  acid 
and  will  therefore  be  discussed  in  detail  in  connection  with  that  acid 
(p.  269).  In  the  laboratory  it  is  generally  made  by  heating  oxalic 
acid  in  glycerol.  The  oxalic  acid  breaks  down  and  yields  formic  acid 
as  will  be  shown  under  oxalic  acid.  When  heated  with  sulphuric 
acid  formic  acid  breaks  down  and  yields  water  and  carbon  monoxide, 
which  is  the  reverse  of  the  second  reaction  just  given. 

H— CO— OH >        CO  +  H— OH 

Formic  acid 


SATURATED   MONOBASIC  ACIDS 


135 


A  study  of  the  general  methods  of  preparation  as  given  under  2,  3, 
and  4  shows  that  formic  acid  is  the  direct  reduction  product  of  carbon 
dioxide,  C02. 

CO2 »    R- COONa 


R— Na 


R— COONa 
H— COONa 
H— COOH 
H—COOH 


General 
reactions 


Sodium  formate 
Formic  acid 
Formic  acid 


R—  ONa  +  CO  — 

H—  ONa  -j-  CO  <- 

H—  OH   +CO  ** 

H—  H      +  CO2  «- 

The  two  reactions  with  carbon  monoxide  become  reversible  at  higher 
temperatures  so  that  when  formic  acid,  is  heated  it  breaks  down  to 
CO  +  H2O  as  just  explained. 

Acetic  Acid    CH3—  COOH    Ethanoic  Acid 

Acetic  Fermentation.  —  Acetic  acid  in  addition  to  its  occurrence  in 
nature  in  the  form  of  esters  is  produced  on  the  large  scale  by  the  acid 
fermentation  (oxidation)  of  the  alcohol  obtained  as  the  result  of  ferment- 
ing fruit  juices  which  contain  sugar,  especially  apple  juice  or  cider, 
and  wine.  When  the  sugar  present  in  cider  is  fermented,  duetto  the 
action  of  the  enzyme  zymase,  alcohol  is  produced  (p.  95).  This  al- 
cohol is  then  oxidized  through  the  activity  of  an  aerobic  bacterial  organ- 
ism Bacterium  aceti,  which  is  present  naturally  in  the  fruit  juice.  The 
product  is  acetic  acid. 

Sugar      +  Zymase    -  >    Alcohol  -f  CO2 

CH3—  CH2—  OH  +  O2  -T*     CH3—  COOH  +  H2O     (Bacterial 


Alcohol 


Acetic  acid 


Vinegar.  —  Acetic  acid  produced  by  this  natural  process  is  known  as 
vinegar.  As  vinegar  may  be  made  by  the  acetic  fermentation  of  any 
natural  alcoholic  liquid  such  as  cider,  wine  or  malt  liquors  it  will  possess 
characteristic  properties  depending  upon  its  source.  Naturally  this 
process  is  slow,  the  cider  being  allowed  to  stand  for  a  long  time  with 
access  to  the  air.  Industrially  the  process  is  much  hastened  by  allow- 
ing the  weak  alcoholic  liquid  to  flow  slowly  over  beech  wood  shavings 
which  are  covered  with  the  bacterium  aceti  while  the  whole  is  kept  well 
aerated  and  at  a  temperature  of  about  33°.  These  processes  all  produce 
a  dilute  solution  of  acetic  acid  known  as  vinegar  which  contains  from 


136  ORGANIC  CHEMISTRY 

about  3.0  to  6.0  per  cent  (cider  vinegar,  U.  S.)  or  6.0  to  12.0  per  cent 
(wine  vinegar,  France)  of  pure  acetic  acid. 

Wood  Distillation. — Acetic  acid  of  greater  strength  than  this  is 
made  by  the  destructive  distillation  of  wood.  This  process  has  been 
described  under  the  preparation  of  methyl  alcohol  (wood  alcohol). 
The  distillate  obtained  from  the  wood  and  known  as  pyroligneous 
acid  contains  about  4  to  8  per  cent  of  pure  acetic  acid.  This  is  separated 
from  the  alcohol,  acetone  and  other  substances  present  by  conversion 
into  the  calcium  or  sodium  salt.  The  acid  is  again  set  free  by  treat- 
ment of  the  calcium  acetate  with  sulphuric  acid  and  is  then  distilled. 
In  this  way  acid  of  about  90  per  cent  is  obtained.  Dilute  acetic  acid 
so  made  is  termed  wood  vinegar.  In  1916  something  over  100,000,000 
pounds  of  acetic  acid  were  produced  from  the  1,100,000  cords  of  wood 
distilled  in  the  U.  S.  which  at  the  same  time  yielded  the  10  to  n  million 
gallons  of  methyl  alcohol  as  given  on  page  95. 

Glacial  Acetic  Acid. — Glacial  acetic  acid  has  the  same  relation  to 
ordinary  acetic  acid  that  absolute  alcohol  has  to  ordinary  alcohol, 
i.e.,  it  is  100  per  cent.  acid.  It  is  obtained  from  strong  acetic  acid  by 
fractional  distillation.  Pure  acetic  acid  crystallizes  at  16.7°,  hence  the 
name  glacial  acetic  acid.  It  is  a  liquid,  boiling  point  120°,  sp.  gr.  1.05, 
with  a  sharp  odor  and  irritating  effect  upon  the  skin  similar  to  formic 
acid  but  not  so  strong.  The  salts  of  acetic  acid  are  mostly  crystalline 
compounds,  the  important  ones  being  those  of  sodium,  potassium, 
ammonium,  calcium,  iron,  aluminium,  copper  and  lead.  The  iron 
and  aluminium  acetates  are  used  as  mordants  in  dyeing.  The  copper 
acetate  is  a  constituent  of  several  insecticides  (Paris  green,  etc.),  and 
the  lead  acetates  are  used  in  medicine  and  in  making  white  lead,  basic 
lead  carbonate,  for  paints.  The  chief  uses  of  acetic  acid  other  than  as 
vinegar  are  in  the  preparation  of  acetone  (p.  133)  and  the  salts  men- 
tioned above.  Also  both  acetic  acid  itself  and  acetone  are  used  in  the 
manufacture  of  smokeless  powder  and  high  explosives. 

Higher  Acids 
The  only  higher  fatty  acids  which  will  be  mentioned  are: 

Butyric  acid,    Butanoic,     C3H7 — COOH,      occurring  as  an  ester 

of  glycerol  in  butter. 

Valeric  acids,  Pentanoic,    C4H9 — COOH,      found  free  and  as  ester 

in  Valeriana  officinalis. 


DERIVATIVES    OF   ACIDS — SALTS,   ACID   CHLORIDES 


Capric  acid,     Hexanoic, 

Palmitic  acid, 

Stearic  acid, 
Arachidic  acid, 


n — COOH,  occurring  as  an  ester 
of  glycerol  in  goat's 
milk. 


,— COOH 


which,  as  esters  of  gly- 
cerol, are  the  chief  con- 
stituents of  many  fats 


Ci7H35-COOH  j 

J  and  oils. 

CigH39 — COOH,  which  occurs  in  peanut 
oil  as  an  ester  of 
glycerol. 


DERIVATIVES  OF  ACIDS 
i.  SALTS  R— COOM 

We  shall  consider  now  several  different  classes  of  compounds  which 
are  formed  from  the  acids,  i.e.,  derivatives  of  the  acids.  The  simplest 
derivatives  are  the  metal  salts  formed  by  neutralizing  the  acid  with  a 
base. 


R— COOH  +  K— OH 

Acid 


R— COOK  +  H2O 

Potassium  salt 


In  these  compounds  the  hydrogen  of  the  hydroxyl  is  replaced  by  a 
metal.  As  there  is  only  one  hydroxyl  hydrogen  in  the  acids  containing 
only  one  carboxyl  group  they  are  mono-basic  and  yield  only  one  class 
of  salts,  viz.,  neutral  salts.  It  will  not  be  necessary  at  this  time  to 
consider  these  compounds  at  any  length  as  they  have  been  sufficiently 
described  under  the  acids  themselves.  The  most  common  acids,  e.g., 
formic  and  acetic  acid,  form  well  crystallized  salts  with  practically 
all  of  the  metals,  and  these  salts  are  all  soluble  in  water.  All  of  these 
salts  on  treatment  with  stronger  acids,  hydrochloric  or  sulphuric, 
yield  the  free  organic  acid. 

2.  ACID  CHLORIDES  R— CO— Cl 
Acetyl  Chloride  CH^-CO— Cl 

The  reaction  which  proves  the  presence  of  the  hydroxyl  group  in 
acids  is  that  with  phosphorus  penta-chloride. 

POC13  +  HC1 


R— CO— OH  +  PCI  5 

Acid 


R— CO— Cl 

Acid  chloride 


The  compound  formed,  R — CO — Cl,  in  which  one  chlorine  atom  has 
replaced  the  acid  hydroxyl,  is  known  as  an  acid  chloride.     The  acid 


138  ORGANIC  CHEMISTRY 

chlorides  may  also  be  formed  by  the  reaction  of  hydrochloric  acid  upon 
the  acid. 

R— CO— (OH  +  H)— Cl    < >    R— CO— Cl  +  H-OH 

Acid  Acid  chloride 

This,  however,  is  not  a  complete  reaction  as  it  is  quickly  reversible,  the 
water  acting  on  the  acid  chloride  reforming  the  acid.  In  fact  this 
reverse  reaction  is  the  more  prominent  and  all  acid  chlorides  form  acids 
when  decomposed  with  water.  With  the  lower  acid  chlorides  the 
action  is  so  violent  that  it  must  be  cautiously  brought  about  and  even 
traces  of  moisture  will  react  so  that  acid  chlorides  fume  when  exposed 
to  the  air.  With  some  of  the  higher  acids  their  chlorides  react  less 
quickly  with  water.  The  ease  with  which  chlorine  in  acid  chlorides  is 
replaced  by  hydroxyl  proves  that  the  union  of  chlorine  in  the  group 
R— CO— Cl  is  different  from  that  in  alkyl  halides,  R— Cl.  The  acid 
radical,  (R — CO — ),  is  known  in  general  as  the  acyl  radical. 

Acyl  Radical. — The  names  of  the  acid  chlorides  are  derived  from 
the  names  of  the  acids  by  changing  the  termination  ic  to  yl.  Thus, 
CH3 — CO — Cl  is  acetyl  chloride  or  ethanoyl  chloride.  The  acid 
chlorides  of  the  lower  acids  are  liquids  which  possess  a  very  penetrating 
and  disagreeable  odor  and  boil  at  a  lower  temperature  than  the  cor- 
responding acid.  Analogous  compounds  of  bromine  and  iodine  are 
formed  by  the  action  of  phosphorus  tri-bromide  or  phosphorus  tri- 
iodide  on  the  acids.  These  are: 

R— CO— Br     Acid  bromide  R— CO— I     Acid  iodide 

The  only  compound  we  shall  mention  is  the  acid  chloride  of  acetic 
acid,  acetyl  chloride,  CH3 — CO — Cl,  ethanoyl  chloride.  This  is  a 
liquid,  boiling  point  51°.  It  is  prepared  by  the  first  method  given. 

Synthetic  Use. — On  account  of  the  activity  of  the  acid  chlorides 
they  are  of  great  importance  as  synthetic  reagents  by  means  of  which 
the  acyl  radical  may  be  united  to  other  radicals.     The  most  important 
reactions  in  which  the  acid  chlorides  are  used  are  the  following: 
(i)  Formation  of  anhydrides  of  the  acids, 

R— CO— (Cl  +  H)— O— OC— R    >    R— CO— O— OC— R  +  HC1 

Acid  chloride  Acid  Acid  anhydride 

(2)  Formation  of  esters, 
R— CO— (Cl  +  H)— OR >        R— CO— OR  +  HC1 

Acid  chloride  Alcohol  Ester 


ACID  ANHYDRIDES  139 

(3)  Formation  of  amides  or  ammonia  derivatives, 
R— CO— (Cl  -f  H)— NH2 >        R— CO— NH2  +  HC1 

Acid  chloride  Acid  amide 

These  reactions  will  now  be  considered  in  connection  with  the  com- 
pounds which  they  form. 

R—  COv 

R 


3.  ACID  ANHYDRIDES  >O 

I—  CCK 


The  acid  anhydrides,  as  just  stated,  are  formed  when  an  acid 
chloride  acts  upon  an  acid,  e.g.,  acetyl  chloride  upon  acetic  acid.  The 
reaction  takes  place  much  better  if  instead  of  the  free  acid  the  sodium 
salt  of  the  acid  is  used, 

CHS—  CO—  (Cl  +  Na)O—  OC—  CH3     --  * 

Acetyl  chloride  Sodium  acetate 

CH3—  CO—  O—  OC—  CH3  +  NaCl 

Acetic  acid  anhydride 

This  is  due  to  the  fact  that  the  other  product  of  the  reaction,  viz., 
sodium  chloride,  does  not  act  upon  the  anhydride  and  cause  a  rever- 
sible action  as  is  true  when  hydrochloric  acid  is  the  other  product. 
As  the  chlorine  of  the  acid  chloride  which  has  replaced  the  hydroxyl 
of  the  acid  removes  the  hydroxyl  hydrogen  from  a  new  acid  molecule  it 
shows  that  the  compound  formed  is  an  anhydride  of  two  molecules  of 
acid, 

CH3—  CO(OH)       -HOH      CH3—  CO 


CH3—  COO(H)  CHr-CO 

Acetic  acid  Acetic  anhydride 

This  is  proven  also  by  the  fact  that  some  anhydrides  may  be  formed  by 
treating  the  acid  itself  with  dehydrating  agents. 

Reaction  with  Water.  —  As  would  be  expected  the  acid  anhydrides 
react  readily  with  water  and  reform  the  acid. 

CH3—  CO  CH3—  CO—  OH 

\)  +  H—  OH         —  > 
CH3—  COX  CH3—  CO—  OH 

Acetic  anhydride  Acetic  acid 

With  Alcohol.  —  As  alcohols  are  water   type  compounds  we  find 
that  the  anhydrides  react  with  them  in  the  same  way  as  with  water, 


140  ORGANIC  CHEMISTRY 

one  of  the  products  being  the  free  acid  and  the  other  the  ester.     This 
gives  another  general  method  of  preparing  the  esters. 

CH3— CO  CHb— CO— OH  Acetic  acid 

\)  +  HO— C2H5       -4 
CH3— COX          Ethyl  alcoho1  CH3— CO— OC2H5  Ethyl  acetate 

Acetic  anhydride  (ester) 

With  Ammonia. — With  ammonia  the  acid  anhydrides  form  amides 
just  as  do  the  acid  chlorides, 

CH3—  COv  CH3— CO— OH  Acetic  acid 

Acetic  anhydride  ^>O  +  H— NH2 > 

CH3— COX  CH3— CO— NH2  Acet-amide 

The  last  two  reactions  will  be  taken  up  again  in  the  following  sections. 
It  will  be  noted  that  in  all  of  the  reactions  of  the  anhydrides  the 
tendency  is  to  reform  the  acid  by  removing  one  hydrogen  from  the  other 
compound  present.  The  remaining  acyl  group  then  unites  with  the 
residue  of  the  reagent  and  a  new  compound  is  formed.  The  character 
of  the  new  compound  depends  upon  the  residue  of  the  reagent.  With 
water  H — OH  we  obtain  the  hydroxyl  compound  of  the  acyl  radical, 
that  is,  the  acid  itself,  while  with  alcohols  we  obtain  the  alkyl-oxy 
compound  of  the  radical,  i.e.,  an  ester,  and  with  ammonia  the  amino, 
( — NH2),  compound  of  the  acyl  radical,  i.e.,  an  amide. 

4.  ESTERS     R— CO— OR     ETHEREAL  SALTS 

The  nature  of  esters  or  ethereal  salts  has  been  fully  discussed  already 
in  connection  with  the  esters  of  inorganic  acids  and  alcohols  (p.  102). 
The  name  salts  applies  because  they  are  formed  by  neutralizing  an 
alcohol,  acting  as  a  base,  with  an  acid.  It  must  be  emphasized,  how- 
ever, that  in  so  terming  these  compounds  salts  we  do  not  mean  this  to 
apply  in  a  physical  chemical  sense  as  describing  their  properties 
in  solution  in  accordance  with  the  electrolytic  theory  of  ionic  disso- 
ciation. We  are  dealing  here  with  questions  of  composition  and 
constitution.  Ethereal  salts  differ  from  metal  salts,  at  least  as  to  the 
degree  of  their  dissociation  into  ions  when  in  solution. 

Esterification. — As  the  organic  acids  which  we  are  considering  con- 
tain only  one  carboxyl  group  they  are  mono-basic,  i.e.,  they  contain 
only  one  acid  hydrogen,  the  hydroxyl  hydrogen,  which  is  replaceable 
by  metals.  They  therefore  react  molecule  for  molecule  with  the 


DERIVATIVES    OF    ACIDS — ESTERS  141 

mono-hydroxy  alcohols  in  the  formation  of  esters.  The  reaction  is 
termed  esterification  and  is  accomplished  by  treating  the  acid  with  the 
alcohol  in  presence  of  some  dehydrating  agent,  e.g.,  sulphuric  acid. 

+  H2S04 
R— CO— O(H  +  HO)— R  -»        R— CO— OR  +  H— OH 

Acid  Alcohol  Esterification  Ester 

The  general  formula  for  esters  of  the  organic  acids  is,  therefore, 
R— CO— OR  or  Acyl-O-Alkyl. 

Hydrolysis. — These  esters  of  the  organic  acids  react  as  those  of  the 
inorganic  acids.  The  most  important  reaction  is  their  decomposition 
with  water  by  which  the  alcohol  and  the  acid  are  reformed.  As  the 
reaction  involves  simply  the  taking  up  of  the  elements  of  water  it  is 
termed  an  action  of  hydrolysis. 

R— CO— 0(R  +  HO)— H >        R— CO— OH  +  R— OH 

Ester  Hydrolysis  Acid  Alcohol 

This  reaction  and  the  preceding  one  are  the  reverse  of  each  other  and 
the  two  may  be  written  as  one  reversible  reaction  as  follows: 

R— COO— (H  +  HO)— R   Esterification   R— CO— O(R  +  HO)— H 

Acid  Alcohol  < —  Ester  Water 

Hydrolysis 

In  the  presence  of  an  alkali  hydrolysis  of  an  ester  yields  not  the  free 
acid  but  the  salt  of  the  acid  and  the  reaction  is  then  non-reversible. 

+  NaOH 
R— CO— O(R    +    HO)— H "    R— CO— ONa  +  R— OH 

Acid  Salt 

Saponification. — As  we  shall  see  later,  this  is  the  kind  of  reaction 
which  takes  place  when  soap  is  made  from  fats  and  on  that  account  it  is 
termed  an  action  of  saponification.  In  this  way  the  acids  are  obtained 
as  salts  from  the  naturally  occurring  fats,  oils  and  waxes  in  which  they 
are  present  in  the  form  of  esters.  The  hydrolysis  of  esters  or  ethereal 
salts  is  then  the  general  reaction  by  which,  with  the  taking  up  of  the  elements 
of  water,  an  ester  is  reconverted  into  the  two  compounds  from  which  it 
was  formed,  viz.,  into  an  acid  and  an  alcohol.  Esterification  and  hydroly- 
sis or  saponification  are,  therefore,  complementary  names  applying 
to  the  reversible  reaction  effecting  the  synthesis  and  decomposition  of 
esters.  The  reversible  character  of  the  reactions  of  esterification  -and 


142  ORGANIC  CHEMISTRY 

hydrolysis  is  shown  by  the  fact  that,  under  different  physical  conditions 
such  as  temperature  and  concentration,  the  amount  of  ester  formed  and 
also  the  rate  at  which  it  is  formed,  i.e.,  the  speed  of  the  reaction,  varies. 
This  makes  the  reaction  a  most  valuable  one  to  study  from  a  physical 
chemical  standpoint.  The  investigation  of  such  problems  as  the  law 
of  mass  action,  chemical  equilibrium,  the  relation  of  constitution  to  the 
speed  of  reaction,  rate  of  esterification  or  degree  or  rate  of  saponification, 
is  greatly  aided  by  the  study  of  the  esters.  These  problems  and  the 
facts  that  have  been  made  known  by  this  study  are  not,  however,  such 
as  we  wish  to  consider  at  this  time  in  a  general  presentation  of  organic 
chemistry. 

Names  of  Esters. — Considering  these  compounds  as  ethereal  salts 
they  are  named  on  the  same  principal  as  metal  salts,  the  name  of  the 
alkyl  radical  being  used  in  place  of  that  of  the  metal.  The  ester  of 
ethyl  alcohol  and  acetic  acid,  CH3COOC2H5,  being  called  ethyl  acetate 
or  ethyl  ethanoate.  Considering  them  as  esters  they  are  named  as 
follows :  ethyl  acetate  is  acetic  acid  ethyl  ester  or  ethanoic  acid  ethane 
ester. 

Isomerism. — Isomerism  in  the  esters  may  be  due  to  several  causes 
analogous  to  those  given  in  the  case  of  the  ethers  and  the  ketones. 

(i)  Isomerism  due  to  the  isomeric  nature  of  the  acyl  or  alkyl  radicals 
present,  e.g.: 


CH3— CH2— CH2— CO— OCH2— CH2— CH3 

Propyl  butyrate 
Butanoic  acid  propane-  i-ester 

CH3— CH2— CH2— CO— OCH— CH3 

CH3 

Iso-propyl  butyrate 
Butanoic  acid  propane-2-ester 

(2)  Isomerism  due  to  different  acyl  or  alkyl  radicals  which  make 
the  total  carbon  content  the  same,  e.g.: 

Ethyl  propionate    CHa— CH2— CO— OCH2— CH3    Propanoic  acid 

ethane  ester 

Methyl  butyrate     CHs—  CH2— CH2—  CO— OCH3    Butanoic  acid 

methane  ester 

Propyl  acetate        CH*— CO— OCH2— CH2— CH3    Ethanoic  acid 

propane  ester 


DERIVATIVES   OF   ACIDS  —  ESTERS  143 

(3)  Isomerism  of  the  esters  with  a  different  group  of  compounds  of 
like  composition,  the  esters  being  isomeric  with  the  acids  of  equal  car- 
bon content,  the  general  formula  for  each  being  CnH2nO2,  e.g.: 

Ethyl  acetate    CH3—  CO—  OCH2—  CH3      Ethanoic  acid  ethane  ester 
Butyric  acid      CH3—  CH2—  CH2—  COOH  Butanoic  acid 

Preparation.  —  There  are  several  very  important  reactions  by  which 
the  esters  may  be  formed. 

(1)  Direct  esterification  of  alcohols  and  acids,  which  is  applicable  in  a 
good  many  cases.     The  presence  of  some  dehydrating  agent  is  neces- 
sary and  sulphuric  acid  is  the  one  usually  employed.    As  sulphuric 
acid  converts  salts  of  the  acids  into  the  acids  it  is  possible  to  use  a  salt 
and  sulphuric  acid  instead  of  the  free  acid. 

R—  CO—  0(Na  +  (H2S04)  +  HO)—  R  --  >  R—  CO-OR  +  H—  OH 

Salt  Alcohol  Ester 

+  NaHSO4 

(2)  From  an  acid  chloride  and  alcohol  as  given  under  the  acid  chlo- 
rides. 

R—  CO—  (Cl  +  H)—  OR    --  >    R—  CO—  OR  +  HC1 

_  Acid  chloride  Alcohol  Ester 

(3)  From  the  anhydrides,  as  stated  in  their  discussion.    As  these 
always  react  with  water  type  compounds,  alcohols  will,  of  course,  yield 
the  ester. 


R—  CO, 


) 

' 


—  OR       ~>    R—  CO—  OR  +  R—  COOH 


T)  _  GO'  Alcohol  Ester  Acid 

Acid 
anhydride 

(4)  From  alkyl  halides  and  the  silver  salt  of  the  acid.  The  silver  halide 
is  formed  and  the  alkyl  radical  takes  the  place  of  the  silver  thus  forming 
the  ester.  This  reaction  shows  clearly  that  the  alkyl  radical  takes  the 
place  of  the  metal  in  the  salt  of  the  acid,  i.e.,  the  ester  is  an  alkyl  salt. 

R—  CO—  O(Ag  +  I)—  R      -  >      R—  CO—  OR  +  Agl 

Silver  salt  Alkyl  Ester 

halide 

Properties  and  Occurrence.  —  The  esters  of  the  lower  acids  and 
lower  alcohols  are  pleasant  smelling  volatile  liquids.  This  property 
is  the  origin  of  the  word  ethereal  in  the  name  applied  to  them.  They 


144  ORGANIC  CHEMISTRY 

are  not  miscible  with  water  though  the  lower  members  are  slightly 
soluble  in  it.  The  higher  esters  are  crystalline  solids  insoluble  in  water 
but  soluble  in  alcohol  and  ether.  While  it  is  probably  true  that  the 
odor  of  common  fruits  is  due  to  the  presence  of  esters  it  is  not  fully 
established  as  they  are  usually  present  in  such  small  quantities. 

Fruit  Flavors. — The  synthetically  prepared  esters  of  some  of  the 
middle  members  of  the  acid  and  alcohol  series  do,  however,  possess 
odors  of  certain  fruits  and  on  that  account  are  prepared  and  used  as 
artificial  fruit  essences  in  perfumery  manufacture  and  as  flavors.  Some 
of  these  artificial  essences  are  as  follows: 

Iso-amyl  iso-valerate,>Iso-valeric  acid  iso-amyl  ester,  Apple  essence 
Ethyl  butyrate,  Butyric  acid  ethyl  ester,  Pineapple  essence 

Amyl  butyrate,  Butyric  acid  amyl  ester,  Apricot  essence 

Iso-amyl  acetate,          Acetic  acid  iso-amyl  ester,  Pear  essence 

Waxes  and  Fats. — The  waxes  are  esters  of  the  higher  alcohols  and  the 
higher  acids  of  the  paraffin  series.  The  fats  are  esters  of  the  higher 
acids  and  a  tri-basic  alcohol,  glycerol.  These  will  be  taken  up  later. 

5.  ACID  AMIDES  R— CO— NH2 

It  will  be  recalled  that  the  primary  amines  are  substitution  products 
of  the  hydrocarbons  in  which  an  ( — NH2)  group,  called  the  amino 
group,  has  been  substituted  indirectly  for  a  hydrogen  of  the  hydro- 
carbon. They  are  prepared  by  treating  an  alkyl  halide  with  ammonia. 

CH3— (Cl    +    H)— NH2        >        CH3— NH2    +    HC1 

Methyl  chloride  Methyl  amine 

Preparation  from  Acid  Chlorides. — If  instead  of  an  alkyl  halide  we 
use  an  acyl  halide,  i.e.,  an  acid  chloride,  a  similar  reaction  takes  place 
with  the  formation  of  a  compound  in  which  the  amino  group  has  re- 
placed the  chlorine. 

CH3— CO— (Cl  +  H)— NH2        >        CH3— CO— NH2  +  HC1 

Acetyl  chloride  Acet-amide 

The  compound  so  formed  is  clearly  one  in  which  the  amino  group  is 
linked  to  the  acyl  group,  the  general  formula  being  R — CO — NH2. 
In  the  original  acid  the  hydroxyl  group  has  been  replaced  by  the 
amino  group.  These  compounds  are  known  as  acid  amides  or  simply 
amides.  The  amide  derived  from  acetic  acid  is  called  acet-amide, 
CH3— CO— NH2. 


ACID    AMIDES  145 

From  Esters. — A  second  method  of  preparation  similar  to  the  first 
is  to  treat  an  ester  with  ammonia.  In  this  reaction  the  alkyl-oxy  radical 
of  the  ester  reforms  alcohol  by  means  of  one  hydrogen  from  the 
ammonia  and  the  acyl  radical  unites  with  the  residue  of  the  ammonia 
yielding  the  amide. 

CH3— CO— (OC2H5  +  H)—  NH2 >  CH3— CO— NH2  +  C2H5— OH 

Ethyl  acetate  Acetamide  Ethyl  alcohol 

From  Ammonium  Salts. — Still  another  method  for  the  preparation 
of  acid  amides  is  to  simply  heat  the  ammonium  salt  of  the  acid.  The 
action  taking  place  has  been  shown  to  result  in  the  loss  of  one  molecule 
of  water. 

-H20 
CH3— CO— ONH4  -»       CH3— CO— NH2        or 

Ammonium  Acetamide 

acetate 

-H2O 
CH3— C— (0)NH2(H2  — >        CH3— C— NH2 

O  O 

Character. — The  amino  substitution  products  of  the  hydrocarbons, 
it  will  be  recalled,  are  strongly  basic  compounds,  alkaline  toward  litmus, 
with  ammoniacal  odor  and  forming  salts  with  acids  analogous  to  ammo- 
nium salts.  The  acid  amides,  however,  are  found  to  be  practically 
neutral  compounds.  We  explain  this  by  saying  that  the  basic  and  acid 
portions  of  the  compound  neutralize  each  other,  the  acyl  radical 
(CH3CO  — )  counteracting  the  ammonia  residue  ( —  NH2) .  That  is,  when 
the  amino  group  is  substituted  in  a  hydrocarbon  so  that  the  nitrogen 
is  linked  to  a  carbon  which  has  only  hydrogen  or  carbon  linked  to  it, 
it  endows  the  resulting  compound  with  a  strong  basic  character. 
When,  however,  the  amino  group  is  substituted  in  the  carboxyl  group 
so  that  the  nitrogen  is  linked  to  a  carbon  united  to  oxygen,  as  carbonyl, 
( — CO — ),  the  basic  character  of  the  amino  group  is  largely,  if  not 
wholly,  neutralized  by  the  acid  character  of  the  acyl  group.  The 
compound  formed  is  neither  basic  nor  acid. 

Reaction  with  Acids. — This  neutral  character  of  the  amides  is, 
however,  similar  to  that  of  the  alcohols,  for,  like  alcohols,  they  act 
as  bases  toward  strong  acids  and  as  acids  toward  strong  bases.  With 
10 


146  ORGANIC  CHEMISTRY 

nitric  acid,  for  example,  acetamide  forms  a  salt  analogous  to  ammo- 
nium salts  in  which  the  nitrogen  becomes  penta-valent. 

CH3—  CO—  NH2  +  HON02        --  >        CH3—  CO—  NH2-HONO2  or 

Acetamide  Acetamide  nitrate 


CH3-CO—  N^J 

\ 
XONO2 

These  salts  are,  however,  readily  decomposed  by  water. 

Reaction  with  Bases.  —  On  the  other  hand,  the  acid  amides  form 
salts  with  strong  bases,  e.g.,  sodium  hydroxide.  The  salt  CH3  —  CO  — 
NHNa  is  known.  Whether  as  in  the  formula  as  written  the  sodium  is 
linked  to  the  nitrogen  seems  doubtful.  To  explain  the  formation  of 
such  a  salt  the  formula  for  acetamide  has  also  been  represented  as 
containing  a  hydroxyl  group,  the  reaction  with  sodium  hydroxide 
being  as  follows: 

CH3—  C—  OH    +    HO—  Na       —  »    CH3—  C—  ONa    +    H2O 
NH  NH 

Acetamide  Sodium  acetamide 

But  the  formation  of  salts  with  strong  acids  and  also  all  of  the  reac- 
tions of  synthesis  go  to  establish  the  formula  for  acetamide  as  first 
given.  We  have  then  two  different  constitutional  formulas  for  acet- 
amide both  of  which  seem  to  be  true. 

CH3—  C—  NH2    <  —  >    and    CH3—  C—  OH 

Acetamide 
O  NH  Tautomeric  forms 

Tautomerism.—  Here  as  in  many  other  instances  which  we  shall 
mention  we  have  a  condition  of  change  in  the  molecule  so  that  at  one 
time  and  toward  certain  reagents  one  formula  is  true,  while  at  another 
time  and  toward  other  reagents  another  formula  is  the  correct  representa- 
tion. This  phenomenon  which  is  not  the  same  as  isomerism  is  known  as 
tautomerism.  It  is  probable  that  the  different  products  formed  by  the 
action  of  silver  cyanide  and  potassium  cyanide  on  alkyl  halides  (p. 
68)  is  to  be  explained  by  tautomerism. 

\  Reactions.  —  The  relation  of  acid  amides  to  water  is  most  impor- 
tant.    They  are  able  to  take  up  the  elements  of  water,  as  in  hydrolysis  ; 


ACID  AMIDES  147 

or,  in  the  presence  of  dehydrating  agents,  they  are  able  to  lose  a  molecule 
of  water.  It  will  be  observed  that  of  the  compounds  studied  those  which 
we  have  shown  take  up  water,  i.e.,  are  hydrolyzed,  are  compounds  con- 
taining the  acyl  radical,  e.g.: 

CH3—  CO, 
CH3—  CO—  OR,          CH3—  CO—  Cl,  )O 

Ester  Acid  chloride  /->TT  _  PO 

Acid  anhydride 

Hydrolysis  of  Acid  Amides.  —  The  amides  are  exactly  analogous  acyl 
compounds,  CH3  —  CO  —  NH2,  and  they  are  quite  easily  hydrolyzed  as 
follows  : 
CH3—  CO—  NH2  +  H—  OH    —  ->    CH3—  CO—  OH  +  NH3    -  > 

Acetamide  Acetic  acid 

CH3—  CO—  ONH4 

Ammonium  acetate 

The  products  are  the  acid  and  ammonia  which  react  forming  the 
ammonium  salt  of  the  acid.  This  is,  of  course,  simply  the  reverse  of 
the  third  method  given  for  preparing  the  amides  (p.  145). 

Dehydration.  —  When  acetamide  is  heated  with  phosphorus  pent- 
oxide,  a  strong  dehydrating  agent,  water  is  lost  and  the  product  is 
methyl  cyanide. 

-H2O 
CH3—  CO—  NH2        -  >        CH3—  CN 

Acetamide  Methyl  cyanide 

This  reaction  indicates  that  the  nitrogen  in  acetamide  is  linked  to  the 
carbon  which  is  in  accord  with  both  of  the  tautomeric  formulas  just 
given.  This  methyl  cyanide,  it  will  be  recalled,  is  readily  hydrolyzed 
to  the  acid  requiring,  however,  two  molecules  of  water.  Acetamide, 
therefore,  is  an  intermediate  step  in  the  hydrolysis  of  an  alkyl  cyanide, 
acid  nitrile,  to  an  acid.  Writing  the  general  reaction  in  steps  we  have, 

R—  CN    +    H2O    —-  >    R—  CO—  NH2    +    H2O    --  > 

Acid  nitrile  Acid  amide 

R—  CO—  OH  +  NH3    --  >    R—  CO—  ONH4 

Acid  Ammonium  salt 

This  double  reaction  was  previously  written  as  single  in  this  way 

H)—  OH 
R—  C(N  +  R  --  >  R—  CO—  OH  +  NH3  --  >  R—  CO—  ONH4 


Acid  nitrile 


Acid  Ammonium  salt 

/ 

H 


148  ORGANIC  CHEMISTRY 

The  inter-relation  between  the  acid  amides,  the  acid  nitriles  and  the 
ammonium  salts  of  the  acids  may  be  represented  as  follows: 


R— CO— NH2 


7 

R—  CO—  ONH4  *-  R—  CN 

-  2H2O     - 

Ammonium  salt  Acid  nitrile 

Hofmann's  Reaction.  —  One  more  important  reaction  of  the  acid 
amides  is  that  known  as  Hofmann's  reaction.  When  an  acid  amide  is 
treated  with  bromine  in  an  alkaline  solution  the  final  product  is  an 
alky  I  ami/ie  containing  one  less  carbon  than  the  amide.  The  steps  in 
the  reaction  are  represented  in  the  case  of  acetamide  as 

+  KOH 
CH3—  CO—  NH2  +  2Br  ~        ~*    CH3—  CO—  NHBr  +  KBr  +  HOH 

Acetamide 


CH3—  CO—  NHBr  +  3KOH  ---  >  CH^NH2  +  KBr  +  K2CO3  +  HOH 

Methyl  amine 

Acetamide  CH*—  CO—  NH2 

The  acid  amides  do  not  have  many  important  representatives  in  this 
series  of  acids.  The  most  important  one  is  acetamide  which  we  have 
used  as  our  illustration  and  which  may  be  formed  by  any  of  the 
methods  given.  The  best  methods  of  preparing  acetamide  are  by 
distilling  a  mixture  of  ethyl  acetate  and  concentrated  ammonium 
hydroxide  or  by  heating  ammonium  acetate  in  glacial  acetic  acid. 
The  latter  is  usually  accomplished  by  heating  a  mixture  of  ammonium 
carbonate  and  glacial  acetic  acid.  The  reactions  involved  in  these 
preparations  are  those  given  above  in  general  methods  (2)  and  (3) 
(p.  145).  Acetamide  is  a  crystalline  solid  which  takes  up  water  in 
the  air  (hygroscopic).  It  melts  at  82°.  When  pure  it  is  odorless, 
but  it  usually  has  a  characteristic  odor  of  a  dead  mouse. 


RECAPITULATION  149 

Recapitulation 

If,  before  proceeding  further,  we  glance  for  a  moment  over  the  ground 
which  we  have  covered  we  see  that  we  have  considered 

1.  The  hydrocarbons  of  the  methane  or  saturated  series. 

2.  The  simpler  mono  substitution  products  of  these  hydrocarbons: 

(a)  Halogen  substitution  products. 

(b)  Amino  substitution  products. 

(c)  Cyanogen  substitution  products. 

(d)  Hydroxyl  substitution  products  or  alcohols. 

3.  Derivatives  of  alcohols : 

(a)  Ethers  (anhydrides). 

(b)  Esters  (ethereal  salts). 

4.  Oxidation  products  of  alcohols : 

(a)  Aldehydes. 

(b)  Ketones. 

(c)  Acids. 

5.  Derivatives  of  acids : 

(a)  Salts. 

(b)  Acid  chlorides. 

(c)  Acid  anhydrides. 

(d)  Esters.    . 

(e)  Acid  amides. 

In  our  discussion  we  have  shown  the  relation  of  the  different  groups  to 
each  other  and  the  reactions  by  which,  in  some  cases,  we  may  pass  from 
one  to  the  other.  Of  the  hydrocarbons  which  are  the  mother  substances 
we  have  considered  only  the  one  series,  viz.,  the  saturated  hydrocarbons 
or  paraffins.  Of  the  substitution  products  or  their  derivatives  we  have 
studied  only  the  simplest  members,  viz.,  the  mono-substitution  products, 
i.e.,  those  resulting  from  the  substitution  in  the  hydrocarbon  chain 
of  only  one  element  or  group.  As  the  substituting  elements  and  groups 
which  we  have  considered  include  all  of  the  more  common  ones  we  may 
say  that  we  have  studied  the  principal  type  compounds  of  the  saturated 
series. 

The  further  treatment  of  the  subject  will  therefore  be  simply  an 
expansion  of  the  general  ideas  which  we  have  been  considering.  Such 
an  expansion  may  proceed  in  either  of  two  directions:  First,  a  considera- 
tion of  other  hydrocarbons  than  those  of  the  methane  or  saturated  series 
and  of  derivatives  obtained  from  them  analogous  to  those  we  have 


150  ORGANIC  CHEMISTRY 

derived  from  methane  and  its  homologues.  Second,  a  consideration  of 
more  complex  substitution  products  resulting  from  the  introduction  of 
more  than  one  like  or  unlike  element  or  group  into  the  hydrocarbon 
chain,  i.e.,  poly-  or  mixed-substitution  products. 

It  seems  better  to  take  up  the  first  line  of  development  and  to  study 
next  those  hydrocarbons  which  differ  from  the  members  of  the  saturated 
series  but  which  are  capable  of  forming  the  same  typical  substitution 
products  and  derivatives.  We  shall  then  be  in  a  position  to  consider, 
irrespective  of  the  character  of  the  hydrocarbon  root,  the  various  com- 
plicated mixed  compounds  or  poly-substitution  products  which  are 
known  and  which  are  of  importance. 


B.  SIMPLER  UNSATURATED  COMPOUNDS 

IV.  UNSATURATED  HYDROCARBONS 

GENERAL 

In  our  discussion  of  the  methane  series  of  hydrocarbons  the  idea 
of  the  saturation  of  the  molecule,  or  rather,  the  saturation  of  the  carbon 
atoms  in  the  molecule,  was  considered  as  one  of  the  essential  and  dis- 
tinguishing characters  of  the  compounds.  Methane,  ethane  and  all 
of  the  hydrocarbons  of  this  series  are  alike  in  being  saturated,  and  this 
saturation  is  shown  by  the  fact  that  none  of  them  are  able  to  take  up, 
by  addition  to  the  molecule,  any  element  or  group  of  elements.  Only 
by  the  reciprocal  process  of  substitution  are  derivatives  formed  from 
these  hydrocarbons.  The  general  formula  for  the  hydrocarbons  of  this 
series  was  shown  to  be  CnH2n+2  and  all  of  the  derivatives,  thus  far  dis- 
cussed, have  resulted  from  the  simple  exchange  of  one  or  more  hydrogen 
atoms  for  an  equivalent  amount  of  another  element  or  elements,  either 
separately  or  as  groups. 

Hydrocarbons  are  known,  however,  which  not  only  have  a  different 
general  formula  from  that  of  the  saturated  hydrocarbons,  but  which 
show,  by  their  properties,  that  they  are  as  distinctly  unsaturated  as 
the  methane  hydrocarbons  are  saturated. 

Ethylene  or  Ethene. — The  hydrocarbon  ethylene  or  ethene  has  the 
composition  C2H4.  This  is  the  first  of  a  new  homologous  series  of 
hydrocarbons  of  the  general  formula  CnH2n,  the  members  of  which 
are  related  to  each  other  in  the  same  way  as  are  the  members  of  the 
methane  series. 

Addition. — When  ethylene,  C2H4,  is  treated  with  hydrobromic  acid, 
or  with  bromine,  it  does  not  act  slowly  as  does  methane  or  ethane,  but 
most  readily,  and  the  resulting  compounds  are  found  to  have  the  com- 
position represented  by  the  formulas  C2H5Br,  and  C2H4Br2.  That  is, 
one  hydrogen  atom  and  one  bromine  atom  or  two  bromine  atoms  are  added 
directly  to  the  hydrocarbon  molecule. 

Unsaturation.— As  the  inability  to  take  up  by  addition  any  other 
element  or  group  of  elements  shows  the  saturation  of  the  carbon  atoms 
in  methane  or  ethane,  so,  in  like  manner,  the  easy  addition  of  hydrogen 


152  ORGANIC  CHEMISTRY 

and  bromine  to  ethylene  shows,  that,  in  it  the  carbon  atoms  must  be 
unsaturated.  When  hydrogen  bromide  is  added  to  ethylene  the  prod- 
uct is  ethyl  bromide,  C2H5Br  monobrom  ethane. 

H   H 

I      I 
C2H4  +  HBr >     C2H5— Br  or  H— C— C— Br 

Ethylene 

H    H 

Ethyl  bromide 

The  reverse  of  this  reaction  also  takes  place  for,  when  an  alkyl 
halide,  especially  the  iodide,  is  heated  with  alcoholic  potassium  hydrox- 
ide, or  is  passed  over  heated  potassium  hydroxide,  hydrogen  iodide  is 
lost,  and  ethylene  is  obtained,  as  follows; 

-HI 
C2H5— I  +  KOH       — »     C2H4 

Ethyl  iodide  Ethylene 

An  analogous  reaction  to  the  above  is  the  one  commonly  used  for 
the  preparation  of  ethylene.  It  consists  in  the  removal  of  the  elements 
of  water  from  ethyl  alcohol  by  heating  with  sulphuric  acid  or  with  zinc 
chloride: 

—  H— OH 
C2H5— OH  +  H2SO4  -*        C2H4 

Ethyl  alcohol  Ethylene 

Constitution  of  Ethylene. — None  of  these  reactions,  however,  show 
anything  in  regard  to  the  constitution  of  ethylene,  for  we  do  not  know, 
in  the  case  of  the  formation  of  ethylene  from  ethyl  iodide  or  from  ethyl 
alcohol,  whether  the  hydrogen  atom  is  removed  from  the  same  carbon 
group  as  the  iodine  or  the  hydroxyl,  or  from  the  other  carbon  group. 
The  reaction  may  be  considered  as  possible  in  either  of  the  following 
ways,  i.e.,  the  hydrogen  and  iodine  may  both  be  removed  from  the 
same  carbon  group  or  from  different  carbon  groups. 

H    H  H    H  H    H 

I      I  -HI         |       |  II 

H— C— C— I       — >     -C— C-         or      H— C— C- 

H     H  H     H  Ethylene  H 

Ethyl  alcohol 


UNSATURATED  HYDROCARBONS  153 

Either  of  the  above  formulas  would  be  possible  as  expressing  the  con- 
stitution of  a  compound  of  the  composition  C2H4.  The  proof  as  to 
which  of  these  is  the  true  one  is  obtained  from  a  study  of  the  product 
formed  from  ethylene  by  the  addition  of  two  bromine  atoms.  When 
bromine  acts  upon  ethylene  the  product,  ethylene  bromide,  C2H4Br2, 
is  found  to  be  the  same  compound  as  one  of  the  two  isomeric  di-brom 
ethanes  which  result  from  the  substitution  of  two  bromine.atoms  for 
two  hydrogen  atoms  in  ethane.  We  have,  then,  the  two  reactions: 

Ethane,      C2H6  +  2Br2       — >     C2H4Br2    +    2HBr    (substitution) 
Ethylene,    C2H4  +  Br2 >     C2H4Br2  (addition) 

Di-brom  ethane 

In  one  case  the  reaction,  is  one  of  substitution,  in  the  other  it  is  one  of 
addition. 

As  previously  discussed  (p.  53),  the  two  di-brom  ethanes  are 
represented  by  the  following  formulas: 

H   H  H    H 

Br— C— C— Br  H— C— C— Br 

II  II 

H    H  H    Br 

Symmetrical  Di-brom  ethane  Unsymmetrical  Di-brom  ethane 

In  one  of  these  compounds  the  two  bromine  atoms  replace  two  hydro- 
gen atoms' in  the  same  carbon  group  giving  an  unsymmetrical  di-brom 
ethane,  while  in  the  other  they  replace  one  hydrogen  atom  in  each 
of  two  carbon  groups  yielding  a  symmetrical  di-brom  ethane. 

The  difference  between  the  two  known  compounds  represented  by 
the  two  formulas  given  above  is  clearly  proven  by  their  reactions.  One 
of  them  when  treated  with  potassium  hydroxide  yields  a  compound 
in  which  the  two  bromine  atoms  are  replaced  by  one  oxygen  atom  and 
the  compound  obtained  is  acet-aldehyde,  which  we  know  has  the 
structure  CH3— CHO 

H    H  H    H 

I  I    ! 

H— C— C— Br  -{-  KOH       »        H— C— C  =  O  +  KBr  +  HBr 

I       I  I 

H     Br  H 

Unsymmetrical  Acet-aldehyde 

Di-brom  ethane 


154  ORGANIC  CHEMISTRY 

Therefore  the  di-brom  ethane  which  yields  acet-aldehyde  must  be  the 
one  in  which  the  two  bromine  atoms  are  linked  to  the  same  carbon 
atom,  i.e.,  the  unsymmetfical  compound.  The  other  compound  then 
must  have  the  two  bromine  atoms  each  linked  to  a  different  carbon 
atom,  i.e.,  it  must  be  the  symmetrical  compound.  Now  it  is  this  last 
compound,  not  the  first,  which  is  obtained  when  ethylene  reacts  with 
bromine  and  adds  on  two  bromine  atoms.  For  this  reason  it  is  known 
as  ethylene  bromide.  Our  reaction  between  ethylene  and  bromine 
must  be  represented,  then,  as  follows : 

H   H 

I      I 
C2H4  +  Br2    »     C2H4Br2  or  BrH2C— CH2Br   or  Br— C— C— Br 

Ethyl-  I        I 

MM 

H   H 

Ethylene  bromide  or  Symmetrical  Di-brom  ethane 

Ethylene  itself,  then,  must  be  represented  by  the  formula: 
H   H  H     H 

— C— C—      or      C  =  C  or  CH2  =  CH2 
H    H  H     H 

Ethylene 

That  is,  it  may  be  considered  as  ethane  from  which  two  hydrogen  atoms 
have  been  removed,  one  from  each  carbon  group  : 

—  2H 
CH3— CH3  -r»          CH2  =  CH2 

Ethane  Ethylene 

This  reaction  does  not  ordinarily  take  place,  but  the  analogous  reac- 
tions, viz.,  the  loss  of  the  elements  of  water  from  ethyl  alcohol,  and 
the  loss  of  hydrogen  and  iodine  from  ethyl  iodide,  do  occur  under  the 
conditions  previously  stated.  The  formation  of  ethylene  by  these 
reactions  may  be  represented  as  follows: 

-  H— OH                                     -  HI 
CH2 — CH2  >  CH2  =  CH2  < CH2 — CH2 

Ethylene 

(H         OH)  (H        I) 

Ethyl  alcohol  Ethyl  iodide 


UNSATURATED  HYDROCARBONS  155 

The  formation  of  addition  products  with  ethylene,  indicating  the 
unsaturated  character  of  the  molecule,  would  naturally  lead  to  the 
idea  that  the  structural  formula  of  the  compound,  in  accordance  with 
its  relation  to  ethane  and  in  accordance  with  our  assumption  that 
carbon  in  organic  compounds  is  tetravalent,  should  be  that  of  ethane 
with  one  valence  bond  of  each  carbon  atom  free  and  unsatisfied, 
-CH2— CH2— . 

Double  Bonds. — However,  the  idea  of  free  unsatisfied  bonds  existing 
in  a  compound  does  not  seem  to  be  natural  and  it  is  therefore,  con- 
sidered as  probable  that  these  free  bonds  tend  to  satisfy  each  other. 
Such  a  molecule  would  contain  two  carbon  groups  with  the  two  carbon 
atoms  doubly,  not  singly  united.  A  double  union,  however,  would 
seem  to  indicate  strength,  whereas,  the  fact  is,  that  ethylene,  in  its 
ready  formation  of  addition  products  and  its  general  reactivity,  shows 
itself  to  be  not  more  but  less  stable  than  ethane.  In  connection  with 
the  tetrahedral  theory  of  the  space  relations  of  carbon  in  organic 
compounds,  and,  as  will  be  shown  more  fully  when  we  consider  the 
cyclic  compounds  in  Part  II,  such  a  double  union  of  two  carbon 
atoms  (or  a  ring  union  of  more  than  two  carbon  atoms),  is  in  fact  a 
less  stable  condition  than  two  carbon  atoms  singly  united.  If  two  car- 
bon atoms,  situated  at  the  center  of  regular  tetrahedra,  become  doubly 
united  by  two  bonds  of  affinity  indicated  by  the  lines  to  the  vertices 
of  the  tetrahedra,  there  must,  of  necessity,  be  a  considerable  strain  pro- 
duced in  bringing  the  double  union  about.  Such' a  strain  would  tend 
to  produce  weakness  rather  than  strength.  This  may  be  indicated 
by  the  following  figures  and  will  be  made  perfectly  plain  by  an  examina- 
tion of  atomic  models. 


\<         H/ 

r\ 


\  / 


Ethane 


FIG.  2. 


156  ORGANIC  CHEMISTRY 

Therefore,  in  accordance  with  the  facts,  viz.,  (a)  unsaturation  and 
instability  of  ethylene.  (b)  .  The  formation  of  ethylene  from  ethyl  alcohol 
by  loss  of  water,  (c)  The  formation  of  ethylene  from  ethyl  bromide, 
or  iodide,  by  loss  of  hydrogen  bromide,  or  iodide,  (d)  The  identity  of 
the  di-brom  addition  product  of  ethylene  (ethylene  bromide),  with  the 
symmetrical  di-brom  ethane  and,  (e)  in  accordance  with  our  conceptions 
of  carbon  in  its  space  relations  and  the  geometric  condition  of  such  space 
arrangement,  the  structural  formula  for  ethylene  has  been  accepted  as 
follows: 


H2O=CH2        or 


Ethylene      TT  TT 

Other  Types  of  Addition.  —  It  may  be  well  to  consider  two  dis- 
tinctly different  cases  of  seeming  unsaturation  as  indicated  by  the 
formation  of  addition  products.  When  ammonia  gas,  or  ammonia 
substitution  products,  viz.,  the  alkyl  amines,  react  with  any  acid, 
e.g.,  hydrochloric  acid,  addition  takes  place  and  the  reaction  is  repre- 
sented as  follows: 

/H  /R 

/H  XR  /^H  /^H 

N^H        or        N^H  +  HCl  -*        N^  —  H    or    N\~  H 

XH  >H  ^H  VH 

Ammonia  Alkyl  amine  \P1  XP1 

Ammonium  Alkyl 

chloride  ammonium 

chloride 

In  this  case  the  addition  of  hydrochloric  acid  is  due  to,  or  produces,  a 
change  in  the  valence  of  the  nitrogen  from  three  in  ammonia  to  five  in  the 
ammonium  salts.  Here,  then,  there  is  no  unsaturation  present. 

Another  example  is  that  of  acetaldehyde,  CH3  —  CHO.     This  com- 
pound as  it  will  be  recalled,  (p.  116)  forms  addition  products  with 
several  substances,  e.g.,  hydrocyanic  acid,  ammonia  and_sodium  acid 
sulphite.     The  reaction  with  hydrocyanic  acid  is  as  follows: 
H  H 

I 
CH3—  C  =  O         +         H—  CN        -  >        CH3—  C—  OH 

Acet-aldehyde  I 

CN 

Aldehyde  hydrogen 
cyanide 


UNSATURATED  HYDROCARBONS  157 

In  these  cases  the  character  of  the  grouping  is  changed  by  the  conversion 
of  a  doubly  linked  carbonyl  oxygen  into  a  singly  linked  hydroxyl  group 
by  means  of  the  hydrogen  of  the  reagent.  The  other  part  of  the  re- 
agent becomes  linked  to  the  carbonyl  carbon  by  the  new  free  valence 
of  the  latter.  In  none  of  the  cases  is  there  either  change  of  valence  or 
unsaturation.  Other  similar  cases  could  be  mentioned  but  these  will 
suffice  to  show  how,  in  the  case  of  ethylene,  addition  reactions  prove 
unsaturation,  while,  in  the  cases  of  ammonia  and  acetaldehyde,  the 
formation  of  addition  products  is  explained  in  other  ways. 

A.  ETHYLENE  OR  ETHENE  UNSATURATED  SERIES 

Saturated  Hydrocarbons 
Methane  Series 


Ethane    CH3—  CH3 
Propane  CH3—  CH2—  CH3 
Butane     CH3—  CH2—  CH2—  CH3 

Unsaturated  Hydrocarbons 
Ethylene  Series 

CnH2n 

CH2  =  CH2  Ethylene  or  Ethene  B.P.  -103° 

CH2  =  CH—  CH3  Propylene  or  Propene  B.P.  48° 

CH2  =  CH—  CH2—  CH3     Butylene  or  Butene-i  B.P.  -5° 

Homologous  Series.  —  Just  as  there  is  a  series  of  hydrocarbons  hom- 
ologous to  methane  each  member  of  which  differs  in  composition  from 
the  preceding  one  by  CH2  so  likewise  there  is  an  homologous  series  of 
hydrocarbons  of  which  the  first  member  is  ethylene.  The  members  of 
this  series  bear  exactly  the  same  relation  to  each  other  as  do  those  of 
the  methane  series,  i.e.,  each  is  the  methyl  substitution  product  of  the 
preceding  member.  Each  contains  one  ethylene  group  of  two  carbons 
linked  by  a  double  bond  and  is  related  to  the  corresponding  member  of 
the  saturated  series  just  as  ethylene  is  to  ethane.  The  general  formula 
for  the  series  is  C«H2n. 

Isomers.  —  The  number  of  possible  isomers  in  the  ethylene  series 
is  greater  than  in  the  saturated  series  as  isomerism  may  be  due  not  only 
to  the  character  oj  the  chain  of  carbons  but  also  to  the  position  of  the 


158  ORGANIC  CHEMISTRY 

double  bond  in  this  chain.  The  systematic  names  of  the  ethylene 
hydrocarbons  correspond  to  those  of  the  saturated  series  with  the  termi- 
nation ane  of  the  latter  changed  to  ene.  The  position  of  the  double 
bond  is  also  indicated  by  a  numerical  suffix.  A  special  sign  is  also 
often  used  to  indicate  the  double  bond,  viz.,  the  capital  Greek  letter 
delta,  A.  Such  cases  of  isomerism  and  also  the  names  of  the  com- 
pounds may  be  illustrated  by  the  hydrocarbons  of  the  composition 
C4H8,  as  follows: 

CH2  =  CH— CH2— CH3  Butene- 1  or  AI— Butene 

CH3—CH  =  CH— CH3    Butene-2  or  A2— Butene 

CH2  =  C — CH3  2-Methyl  propene-i  or  2-Methyl  AI— propene 

CH3 

Chemical  Properties. — The  chemical  properties  of  the  ethylene 
hydrocarbons  are,  in  all  cases,  like  those  of  ethylene  itself.  They  are 
more  unstable  than  the  corresponding  members  of  the  saturated  series. 
This  instability  is  especially  shown  by  their  tendency  to  form  addi- 
tion products  by  taking  up  directly,  without  substitution,  two  and  only 
two  halogen  atoms  and  forming,  thereby,  the  di-halogen  substitution 
products  of  the  corresponding  saturated  hydrocarbon.  Not  only  do 
the  unsaturated  hydrocarbons  form  these  addition  products  with  the 
halogens,  but,  in  some  cases,  with  hydrogen  itself,  thereby  being  con- 
verted into  the  corresponding  saturated  hydrocarbon.  With  the  halo- 
gen binary  acids  the  mono-halogen  alky  Is  are  formed.  With  water 
the  unsaturated  hydrocarbons  yield  the  saturated  hydroxy  compounds 
or  alcohols.  The  ethylene  hydrocarbons  are  oxidizable  with  potassium 
permanganate  or  chromic  acid,  but  yield,  by  such  oxidation,  acids 
poorer  in  carbon  than  the  hydrocarbon.  In  this  case  the  ethylene 
group,  the  double  linked  carbons,  is  destroyed  yielding  carbon  di-oxide. 
When  heated  they  are  all  liable  to  decompose  and  polymerize. 

Ethylene    CH2  =  CH2    Ethene 

The  only  member  of  this  series  to  be  considered  in  detail  is  the  first 
member  ethylene  or  ethene,  C2H4  or  CH2  =  CH2.  It  is  most  readily 
prepared  by  heating  ethyl  alcohol  with  an  excess  of  sulphuric  acid.  In 
the  preparation  of  ethyl  ether  equal  molecular  parts  of  ethyl  alcohol 


UNSATURATED  HYDROCARBONS  159 

and  sulphuric  acid  are  heated  to  140°  and  then  more  alcohol  is  added, 
ether  being  produced.  The  reactions  taking  place  are  as  follows: 

C2H5— (OH  +  H)0— SO2— OH     >      C2H6— O— SO2— OH  +  H2O 

Ethyl  alcohol  Ethyl  sulphuric 

acid 

C2H5— (O— S02— OH  +  H)0— C2H5   >    C2H5— O— C2H5  +  H2SO4 

Ethyl  ether 

If,  however,  double  molecular  proportions  of  sulphuric  acid  are  used 
and,  at  160°,  additional  sulphuric  acid  and  alcohol  are  added,  the  first 
reaction  above  is  the  same  then,  with  the  excess  sulphuric  acid,  the  ethyl 
sulphuric  acid  yields  ethylene  and  sulphuric  acid  is  regenerated,  as 
follows  : 

C2H6— O— SO2— OH  — *  C2H4  +  H2SO4 

or 
CH2— CH2 

|  »  CH2=CH2  +  H2S04 

(H        O— SO2— OH)  Ethylene 

Ethyl  sulphuric  acid 

In  effect,  the  reaction  is  simply  the  loss  of  wafer  from  one  molecule  of 
alcohol,  viz., 

-H— OH 
CH2 — CH2  >  CH2  =    CH2 


Ethylene 


(H        OH) 

Ethyl  alcohol 


Ethylene  is  a  colorless  gas  that  burns  with  a  smoky  flame.  It  boils 
at— 103°  (750  m.m.)  and  is  liquefied  at  — 1.1°  at  42  atmospheres 
pressure.  When  heated  it  decomposes  and  polymerizes  yielding  vari- 
ous products,  e.g.,  CH4,  C2He,  C6H6,  etc.  It  is  commonly  known  as 
olefiant  gas  and  is  obtained  when  numerous  organic  substances  are 
heated.  It  forms  explosive  mixtures  with  oxygen. 

B.  ACETYLENE  OR  ETHINE  UNSATURATED  SERIES 

It  has  been  shown  how,  by  a  loss  of  two  hydrogen  atoms,  the  hydro- 
carbons of  the  saturated,  or  methane,  series  are  converted  into  ethyl- 
ene unsaturated,  or  doubly  linked  compounds.  By  a  further  loss  of 


l6o  ORGANIC  CHEMISTRY 

two  hydrogen  atoms  from  the  molecule  a  series  of  hydrocarbons  is 
obtained  possessing  still  greater  unsaturation,  as  follows: 

- 2H  - 2H 

Saturated  Ethylene  Acetylene 

series  series  series 

-  2H                         -  2H 
C2He  >         C2H4          >         C2H2 

Ethane  Ethylene  Acetylene 

Ethene  Ethine 

Just  as  ethylene,  because  of  its  unsaturation,  readily  takes  up  two 
mono-valent  atoms,  forming  addition  products,  and  thereby  passing 
over  to  the  saturated  series,  so  it  has  been  found  that  acetylene,  or 
ethine,  readily  takes  up,  by  addition,  either  two  or  four  mono-valent 
atoms.  In  the  first  case  it  passes  to  the  more  nearly  saturated  ethyl- 
ene series  and  then  to  the  fully  saturated  or  methane  series.  This 
relationship  may  be  shown  by  the  following  scheme: 

C2H4      -f-      2H          *         C2Hg 

Ethene  Ethane 

C2H4      +      HI          >        C2H5I 

Ethene  Ethyl  iodide 

lodo  ethane, 

C2H2        -}-         2H  >  C2H4 

Ethine  Ethene 

C2H2      +      HI          >        C2H3I 

Ethine  Mono-iodo  ethene 

C2H2      +      4H          >        C2H6 

Ethine  Ethane 

C2H2      +      2HI         >       .C2H4I2 

Ethine  Di-iodo  ethane 

Triple  Bond. — The   structural  formula  for  acetylene,  or  ethine, 
analogous  to  that  of  ethene  is  represented  as  follows: 

C2H2    or    HC  =  CH    Acetylene,  Ethine 

That  is,  in  acetylene  the  two  carbon  atoms  are  triply  linked  and  this 
constitution  agrees  with  its  reactions,  with  its  unsaturation  and  with 
the  amount  of  this  unsaturation.  It  has  also  been  established  by  a 
similar  series  of  reaction  to  those  discussed  in  proving  the  symmet- 
rical, double  bond  formula  for  ethylene.  Acetylene  may  be  formed 
from  ethane  and  its  derivatives  and  also  from  ethylene  and  its  deriva- 
tives by  the  reverse  of  the  reactions  cited  above,  or  analogous  ones. 
Homologous  Series,  Names. — The  homologous  members  of  the 
acetylene  or  ethine  series  of  hydrocarbons  are  related  to  each  other  ex- 


UNSATURATED  HYDROCARBONS  l6l 

actly  as  are  those  of  the  methane  and  ethylene  series,  i.e.,  each  hydro- 
carbon is  the  methyl  substitution  product  of  the  one  preceding.  Each 
compound  also  con  tains  one  group  of  two  carbons  linked  by  a  triple  bond. 
The  systematic  names  take  the  termination  ine  which  in  official 
nomenclature  of  the  aliphatic  hydrocarbons  always  signifies  an  unsatu- 
rated  compound  with  a  triple  bond  or  acetylene  group  just  as  ene  sig- 
nifies an  unsaturated  compound  with  a  double  bond  or  ethylene  group 
and  ane  a  saturated  compound  with  only  singly  linked  carbons.  Con- 
sidering briefly  the  relation  between  the  three  series  of  hydrocarbons 
which  have  thus  far  been  discussed  it  may  best  be  shown  by  the  fol- 
lowing tabular  arrangement  of  the  first  four  members  of  each  series. 

Saturated  Hydrocarbons  Unsaturated       Hydrocarbons 

Methane  Series  Ethylene  Series  Acetylene  Series 

General 

formula   CnH2n  +  2  C«H2n  CBH2n_  2 

C2       C2H6  C2H4  C2H2 

CHs— CH.i  CH2  =  CH2  CH  =  CH 

Ethane  Ethene  Ethine 

C3      C»H8  C3H«  C3H4 

CHa— CHj— CHs  CH2  =  CH— CHS  CHsC— CH3 

Propane  Propene  Propine 

C4      C4Hio  C4H8  C4H« 

CHs— GHz— CH2— CH3     CH2=  CH— CHr-CHj  CH  =  C— GHz— CHs 

Butane  Butene-i  Butine-i 

CHj— CH  =  CH— CH3  CHj—  C  =  C— CHa 

Butene-2  Butine-2 

CH»— CH— CH,  CH,  -  C— CHa 

I  I 

CH3  CH3 

2-Methyl  propane  2-Methyl  propene 

These  three  series  include  all  of  the  more  common  hydrocarbons  be- 
longing to  what  are  termed  open  chain  or  a-cyclic  (non-cyclic)  com- 
pounds. Furthermore,  almost  all  of  the  derived  compounds  here 
studied  are  derivatives  of  hydrocarbons  belonging  to  one  of  these  series. 

Acetylene        CH  =  CH        Ethine 

This  hydrocarbon  is  the  first  member  and  gives  its  name  to  the  series. 
It  was  discovered  by  Davy  in  1836  and  was  synthesized  from  the  ele- 
ments and  its  constitution  established  by  Berthelot  in  1859.  It  is 
formed  when  organic  compounds  are  incompletely  oxidized,  as  when  a 
Bunsen  burner  strikes  back  and  gives  off  a  gas  with  a  characteristic 
11 


1 62  ORGANIC  CHEMISTRY 

odor.  It  is  a  colorless  gas  that  burns  with  a  brilliant  flame  giving  a 
very  satisfactory  light.  It  is  often  used  for  illumination  purposes  with 
specially  designed  lamps  or  in  connection  with  small  generators.  For 
this  purpose  it  is  made  from  calcium  carbide,  CaC2,  by  the  action  of 
water. 

CaC2        +        H2O        >        C2H2        +        CaO 

Calcium  carbide  Acetylene 

An  important  property  of  acetylene  is  the  ease  with  which  it  forms 
metallic  compounds  especially  with  copper  and  with  silver.  These 
compounds  are  explosive  both  by  heat  and  by  detonation.  In  many 
of  the  explosive  accidents  .in  connection  with  acetylene  gas  plants  the 
cause  has  been  the  formation  of  these  metallic  compounds. 

C.  DI-ETHYLENE  HYDROCARBONS— DI-ENES 

Isoprene. — Isomeric  with  the  acetylene  series  of  hydrocarbons  are 
those  which  contain  not  one  but^wo  sets  of  doubly  linked  carbon  atoms. 
As  each  additional  bond  between  carbons  means  the  loss  of  two  hydro- 
gen atoms,  then  two  double  bonds  and  one  triple  bond  will  be  equivalent 
and  will  represent  a  loss  of  four  hydrogen  atoms  from  the  saturated 
hydrocarbon.  Therefore  the  general  formula  is  CnH2n_2.  Hydro- 
carbons containing  two  pairs  of  doubly  linked  carbons  or  ethylene 
groups  are  termed  di-ethylenes  or  di-enes.  The  only  compound  to  be 
mentioned  contains  five  carbons,  and  is  known  as  isoprene,  CsHg.  Its 
constitution  has  been  established  as  a  four  carbon  chain  with  a  sub- 
stituting methyl  linked  to  carbon  2  and  with  double  bonds  at  carbons 
i  and  3,  as  follows: 

CH2  =  C  -  CH  =  CH2    Isoprene 

CH3  2-M ethyl  buta-i-3-di-ene 

Isoprene  is  of  especial  importance  in  connection  with  the  terpenes  as  it 
has  been  shown  to  be  the  mother  hydrocarbon  of  caoutchouc  or  rubber. 
Its  constitution  and  properties  will  be  discussed  again  later  on. 

D.  HYDROCARBONS  OF  GREATER  UNSATURATION 

While  most  of  the  compounds  commonly  met  with  are  derivatives 
of  one  of  the  three  series  of  hydrocarbons  which  have  been  studied  it 
should  be  mentoned  that  hydrocarbons  are  known  which  possess  still 


UNSATURATED  HYDROCARBONS  163 

greater  unsaturation  than  exists  in  those  of  the  general  formulas 
CnH2n  and  CnH2n_2.  As  the  loss  in  hydrogen  is  by  twos,  compounds 
of  greater  unsaturation  would  be  expressed  by  the  formulas  CnH2n-4, 
CnH2n-6,  etc.  Considering  the  formulas  for  ethylene  and  acetylene, 
viz.,  CH2  =CH2  and  CH  =  CH,  we  see  that  a  hydrocarbon  of  two 
carbon  atoms  cannot  exist  with  unsaturation  beyond  CnH2n-2,  as  in 
the  case  of  acetylene.  The  loss  of  two  more  hydrogen  atoms  from  it 
would  leave  simply  elemental  carbon.  It  is  plain,  therefore,  that  the 
only  way  in  which  greater  unsaturation  can  result  is  by  increasing  the 
number  of  doubly  or  triply  linked  groups.  As  in  the  case  of  isoprene, 
two  doubly  linked  groups  are  equivalent  to  one  triply  linked  group  so  a 
compound  of  the  formula  CnH2n_4  must  contain  three  doubly  linked 
groups,  and  one  of  the  composition  CnH2n_e  may  have  two  triply 
linked  groups.  Only  one  hydrocarbon  of  each  of  these  highly  unsatu- 
rated  series  will  be  mentioned.  The  one  of  the  composition  C»H2n-4 
has  the  empirical  formula  CioHie  and  is  important  because  it  is  iso- 
meric  with  the  terpenes  (Pt.  II).  Its  constitution  has  been  established 
as  an  eight  carbon  chain  with  two  methyl  groups  substituted  in  carbons 
3  and  7  and  with  three  double  bonds  at  carbons  i,  2  and  4.  It  is  thus 
a  tri-ene.  Its  formula  and  systematic  name  are,  therefore, 

CH2  =  C  =  C— CH  =  CH— CH2— CH— CH3     3~7-I>i-methylocta-i- 

2-4-tri-ene 
CH3  CH3 

Di-propargyl. — The  hydrocarbon  with  the  general  formula  CnH2n_6 
has  the  composition  C6H6  and  is  known  as  di-propargyl.  It  has  been 
shown  to  contain  two  triple  bonds  and  is  thus  a  di-ine.  Its  constitution 
has  been  established  as  a  straight  chain  of  six  carbons  with  the  triple 
bonds  at  carbons  i  and  5.  Its  formula  is 

Di-propargyl        CH  =  C— CH2— CH2— C  =  CH        i-5-Hexa-di-ine 

It  is  known  as  di-propargyl  because  the  group  (CH  =  C — CH2 — )  is 
called  propargyl  (p.  167).  The  compound  is  of  importance  because 
it  is  isomeric  with  benzene  which  is  a  cyclic  or  closed  chain  hydrocarbon 
and  the  mother  substance  of  a  large  series  of  compounds  constituting 
Part  II  of  this  book. 


V.  MONO-SUBSTITUTION     PRODUCTS     OF     UNSATURATED 
HYDROCARBONS 

A.  HALOGEN  AND  CYANOGEN  SUBSTITUTION  PRODUCTS 

The  mono-halogen  substitution  products  of  the  ethylene  series  of 
hydrocarbons  are  of  two  classes.  These  may  be  best  illustrated  with 
the  hydrocarbon  propene,  CH2  =  CH — CH3.  In  such  a  hydrocarbon 
containing  a  double  bond,  substitution  may  take  place  either  in  a  car- 
bon which  is  not  doubly  linked  or  in  one  of  the  two  which  is  doubly 
linked.  In  the  former  case,  as  in  the  compound  CH2  =  CH — CH2C1, 
3-chlor  propene,  the  compound  resulting  is  a  true  analogue  of  the 
substitution  products  of  the  saturated  hydrocarbons.  The  chlor 
propene  above  is  like  the  alkyl  halides  and  as  such  yields  alcohols, 
amines,  cyanides,  etc.,  when  treated  with  silver  hydroxide  or  potas- 
sium hydroxide,  with  ammonia  or  with  potassium  cyanide.  When, 
however,  a  halogen  is  substituted  in  one  of  the  carbons  which  is  doubly 
linked  as  in  CHC1  =  CH— CH3,  i-chlor  propene,  or  CH2  =  CC1— CH3, 
2 -chlor  propene,  then  the  compound  is  not  like  the  alkyl  halides  and  does 
not  yield  an  alcohol,  amine  or  cyanide  as  in  the  former  case.  When 
such  a  halide  is  treated  with  potassium  hydroxide  it  loses  the  halogen 
and  one  hydrogen  and  is  converted  into  a  hydrocarbon  of  the  ethine 
series,  as  follows: 

-HC1 
CH  =  C— CH3  +  KOH  — »        CH  =  C— CH3 

Propine 

(Cl      H) 

i -Chlor  propene 

VINYL  HALIDES— HALOGEN  ETHENES 

Vinyl  Chloride. — As  ethylene  or  ethene  contains  doubly  linked  car- 
bons only,  substitution  of  halogen  will  result  in  a  compound  of  the  sec- 
ond class  given  above. 

CH2  =  CHC1  CH2  =  CHBr 

Vinyl  chloride  Vinyl  bromide 

Chlor  ethene  Brom  ethene 

The  radical  (CH2  =  CH — )  is  known  as  vinyl. 

164 


UNSATURATED   HALIDES,   CYANIDES,   ETC.  165 

ALLYL  HALIDES,  CYANIDES,  ETC. 

Allyl  Chloride. — The  halogen  substitution  products  of  propene  and 
the  higher  hydrocarbons  of  the  ethene  series,  when  the  substitution  is 
in  a  carbon  group  not  doubly  linked,  are  of  importance  in  the  synthesis 
of  derivatives  in  the  same  way  as  are  the  alkyl  halides.  3 -Chlor  propene 
or  propenyl  chloride,  CH2  =  CH — CH2C1,  is  known  also  as  allyl  chloride, 
the  radical  (CH2  =  CH — CH2 — )  being  known  as  allyl. 

Allyl  Cyanide,  Iso-thio-cyanate,  etc. — From  allyl  chloride  or  the 
iodide  there  may  be  prepared  by  the  customary  reactions  allyl  cyanide 
and  other  of  the  cyanogen  compounds.  With  potassium  cyanide  allyl 
iodide  yields  allyl  cyanide.  The  reaction,  however,  instead  of  yielding 
a  cyanide  of  the  expected  constitution  is  accompanied  by  a  shifting  of 
the  double  bond  to  the  second  carbon  so  that  the  cyanide  has  a  con- 
stitution unlike  that  of  the  iodide  from  which  it  is  made. 
CH2  =  CH— CH2— (I  +  K)— CN  > 

Allyl  iodide 

CH2  =  CH— CH2— CN        >        CH3— CH  =  CH— CN 

Allyl  cyanide 

This  is  proven  by  the  fact  that  allyl  cyanide  on  hydrolysis  yields 
crotonic  acid  in  which  the  double  bond  is  at  carbon-2  (p.  173).  Of 
the  other  cyanogen  derivatives  of  propene  the  following  are  known 
though  the  position  of  the  double  bond  is  not  established  in  all  cases. 

Allyl  iso-cyanide  CH2  =  CH— CH2— N  =  C    or 

CH2  =  CH— CH2— N  =  C 
Allyl  thio-cyanate  CH2  =  CH— CH2— S— C=N 
Allyl  iso-thio-cyanate  CH2  =  CH— CH2— N  =  C  =  S    Oil  of  Mustard 

Oil  of  Mustard. — Only  the  last  compound  named  is  important, 
viz.,  allyl  iso-thio-cyanate,  CH2  =  CH— CH2NCS.  Strange  as  it 
may  seem,  from  statements  made  in  connection  with  the  cyanates 
and  iso-cyanates  of  the  saturated  series,  this  compound  is  made  by 
treating  allyl-iodide,  not  with  silver  thio-cyanate,  but  with  potas- 
sium thio-cyanate.  As,  however,  the  tautomeric  iso-compounds  are 
made  from  the  cyanates  and  thio-cyanates  by  heat,  the  conversion  of 
the  first  formed  thio-cyanate  into  the  iso-thio-cyanate  can  readily  be 
understood. 
CH2  =  CH— CH2— (I  +  K)SCN  > 

Allyl  iodide 

CH2  =  CH— CH2SCN  +  heat         >         CH2  =  CH— CH2— NCS 

Allyl  thio-cyanate  Allyl  iso-thio-cyanate 


1 66  ORGANIC  CHEMISTRY 

Allyl  iso-thio-cyanate  is  found  in  nature  as  a  glucoside  constit- 
uent of  mustard  seed.  It  is  known,  therefore,  as  mustard  oil.  It  is 
a  liquid  with  a  sharp  odor  and  with  a  boiling  point  of  1 50.7°.  The  proof 
that  it  is  iso-thio-cyanate  is  its  conversion  into  allyl-amine,  CH2  = 
CH— CH2NH2. 

B.   UNSATURATED  ALCOHOLS 
I.  ETHYLENE  SERIES     (CnH2n_,)— OH 

As  primary  alcohols  must  contain  the  group  ( — CH2 — OH),  it  is 
plain  that  the  simplest  primary  alcohol  of  the  ethylene  hydrocarbons 
must  be  derived  from  the  first  hydrocarbon  of  this  series  which  con- 
tains a  methyl  group.  This  will  be  the  three  carbon  member,  viz., 
propene,  CH2  =  CH — CH3.  As  ethene,  CH2  =  CH2,  contains  no  such 
methyl  group  it  can  not  yield  a  primary  alcohol. 

Vinyl  Alcohol    CH2  =  CH— OH    Ethen-ol 

The  only  hydroxyl  substitution  product  of  ethene  which  is  possible, 
and  the  only  one  known,  has  the  constitution  represented  by  the  above 
formula  and  is  plainly  a  secondary  alcohol  as  it  contains  the  secondary 
group  (  =  CH — OH).  It  may  be  produced  by  the  oxidation  of  ethyl 
ether  by  means  of  chromic  acid,  Cr03,  ozone,  or  even  by  air  when  in  the 
sunlight. 

CH3— CH2— O— CH2— CH3  +  02      >      2CH2  =  CH— OH  +  H2O 

Ethyl  ether  Vinyl  alcohol 

Ethen-ol 

Allyl  Alcohol    CH2  =  CH— CH2— OH    A^open-ol-a 

This  simplest  primary  alcohol  of  the  ethylene  series,  and  commonly 
known  as  allyl  alcohol,  is  produced  from  glycerol  (glycerin)  by  a  re- 
action which  will  be  discussed  later.  It  is  also  produced  by  the 
destructive  distillation  of  many  organic  substances,  such  as  wood,  and 
is  therefore  found  as  a  constituent  of  crude  wood  alcohol.  It  is  a 
colorless  liquid  with  a  strong  odor  and  it  boils  at  96.6°.  It  mixes  in  all 
proportions  with  water.  By  the  action  of  nascent  hydrogen,  Zn  -f- 
H2SO4,  it  is  converted  into  the  corresponding  saturated  alcohol: 

CH2  =  CH— CH2— OH  +  H2       >       CH3— CH2— CH2— OH 

Ai-Propen-ol-3  Propan-ol-i 


UNSATURATED  ALCOHOLS,  ALDEHYDES  AND  ACIDS     167 

Higher  Ethylene  Alcohols 

Geraniol. — Alcohols  derived  from  higher  hydrocarbons  of  the  ethyl- 
ene  series  are  known.  The  most  important  one  is  derived  from  a  di-ene 
containing  ten  carbons  and  belongs  to  a  class  of  compounds  known  as 
terpenes  which  will  be  considered  later  (Pt.  II).  It  is  called  geraniol 
and  has  the  following  constitution. 

CH3— C  =  CH— CH2— CH2— C  =  CH— CH2OH         Geraniol 
CH3  CH3 

II.  ACETYLENE  SERIES  (CnH2n_3)— OH 

Propargyl  Alcohol. — Only  one  alcohol  of  this  series  will  be  con- 
sidered. The  simplest  primary  alcohol  possible  derived  from  hydro- 
carbons of  the  acetylene  series  is  the  one  derived  from  allylene,  CH  = 
C— CH3,  methyl  acetylene. 

CH  =  C— CH,  CH  =  C— CH2— OH 

Allylene  Propargyl  alcohol 

Propine  Ai-Propin-ol-j 

We  have  referred  to  this  alcohol  (p.  163)  in  connection  with  the  un- 
saturated  di-ine  hydrocarbon  I -5-hexa-di-ine,  CH  =  C — CH2 — CH2 
— C  =  CH,  which  is  known  as  di-propargyl  because  it  contains  two  of 
the  groups  present  in  the  above  alcohol,  i.e.,  the  propargyl  radical 
(CH  =  C  -  CH2— ). 

C.  ETHERS  AND  THIO-ETHERS 

Thio-ethers.— Ethers  derived  from  the  unsaturated  hydrocarbons 
are  known  but  are  not  important.  The  corresponding  sulphur  com- 
pounds, viz.,  the  thio-ethers,  are,  however,  of  considerable  importance 
and  are  represented  by  a  commonly  occurring  substance.  The  thio- 
ether  related  to  allyl  alcohol  is  known  as  allyl  thio-ether,  or,  also  as 
allyl  sulphide.  It  is  made,  like  the  thio-ethers  of  the  saturated  series, 
by  treating  the  iodide  of  the  hydrocarbon  with  potassium  sulphide. 

CH2  =  CH-CH2(I  CH2  =  CH-CH2\ 

CH2  =  CH— CH2(I  4  CH2  =  CH— CH2/ " 

Allyl  iodide  Allyl  thio-ether 

Allyl  sulphide 


1 68  ORGANIC  CHEMISTRY 

Oil  of  Garlic. — This  compound,  usually  known  by  the  latter  name, 
allyl  sulphide,  is  a  constituent  of  oil  of  garlic  and  is  a  liquid  with  an 
odor  resembling  that  of  garlic. 


D.  UNSATURATED  ALDEHYDES 

• 

The  aldehydes  of  the  ethylene  series  which  result  from  the  alcohols 
by  oxidation,  and  the  acids  which  are  the  oxidation  products  of  the  alde- 
hydes, both  contain  several  important  naturally  occurring  members. 

Acrylic  Aldehyde    CH2  =  CH—  CHO    Acrolein 

When  allyl  alcohol,  Ai-propen-ol-3,  is  oxidized  carefully  allyl 
aldehyde  is  obtained.  As  this  aldehyde  yields  acrylic  acid  on  further 
oxidation  it  is  more  commonly  known  as  acrylic  aldehyde  and  also  as 
acrolein. 

CH2  =  CH—  CH2—  OH  +  O        -  >        CH2  =  CH—  CHO  +  H2O 

Allyl  alcohol  Acrylic  aldehyde 

Ai-Propen-ol-3  Propen-al 

We  have  mentioned  the  fact  that  allyl  alcohol  is  formed  from  glycerol, 
the  reaction  for  which  will  be  considered  later.  Similarly,  allyl  alde- 
hyde, or  acrylic  aldehyde,  is  obtained  when  glycerol  is  heated.  Fats 
being  glycerol  derivatives,  as  we  shall  see  when  we  study  this  compound, 
they,  too,  on  heating  yield  acrylic  aldehyde.  It  is  a  volatile  liquid 
boiling  at  52.4°,  with  a  sharp  odor  which  is  very  penetrating  and  which 
acts  upon  the  eyes  causing  the  flow  of  tears.  Hence,  when  fats  or 
glycerol  are  strongly  heated  a  sharp  odor  is  noticed  due  to  the  formation 
of  acrylic  aldehyde.  The  aldehyde  on  reduction  with  hydrogen  yields, 
first,  allyl  alcohol  which,  on  further  action  of  hydrogen,  yields  propyl 
alcohol. 

CH2;=  CH—  CHO  +  H2    -  >     CH  =  CH—  CH2—  OH  +  H2    --  > 

Acrylic  aldehyde  Allyl  alcohol 

Ai-Propen-ol-3 

CH3—  CH2—  CH2—  OH 

Propyl  alcohol 
Propan-ol  -i 

Similarly,  on  addition  of  hydrochloric  acid,  the  aldehyde  yields  chlor" 
propionic  aldehyde,  or  3-chlor-propan-al. 


2  =  CH—  CHO      +      HC1        -  >        CH2C1—  CH2—  CHO 

Propen-al  3-Chlor  propan-al 


UNSATURATED  ALCOHOLS,  ALDEHYDES  AND  ACIDS     169 

Thus  the  unsaturated  character  of  the  hydrocarbon  chain  and  the 
presence  of  the  aldehyde  group  are  both  proven.  As  an  aldehyde,  it 
also  forms  addition  products  with  ammonia,  hydrogen  cyanide  and 
sodium  acid  sulphite. 

Crotonic  Aldehyde    CH3—  CH  =  CH—  CHO    A2-Buten-al 

The  aldehyde  derived  from  the  next  higher  hydrocarbon  of  the  ethyl- 
ene  series,  viz.,  the  four  carbon  hydrocarbon,  butene,  is  known  as 
crotonic  aldehyde  because  on  oxidation  it  yields  an  acid  known  as 
crotonic  acid.  As  there  are  two  isomeric  butenes  due  to  the  position 
of  the  double  bond  there  will  likewise  be  possible  two  isomeric  alde- 
hydes or  butenals. 


CH3—  CH  =  CH—  CH3        -  >        CH3—  CH  =  CH—  CHO 

A2-Butene  A..-Buten-al 

CH2  =  CH—  CH2—  CH3  —  »        CH2  =  CH—  CH2—  CHO 

Ai-Butene  Ai-Buten-al 

Now  the  aldehyde  which  yields  crotonic  acid  on  oxidation,  i.e.,  crotonic 
aldehyde,  may  be  prepared  by  a  synthesis  which  shows  clearly  that  it 
must  have  the  constitution  of  the  first  of  these  isomeric  aldehydes, 
A  2-buten-al,  CH3—  CH  =  CH—  CHO. 

Aldol  Condensation.  —  In  discussing  the  addition  products  formed 
from  acetaldehyde  (p.  116),  it  was  stated  that  it  forms  a  condensation 
product  with  a  second  molecule  of  itself.  The  product  is  aldol,  the 
reaction  being  known  as  the  aldol  condensation. 

H  H 

CH3—  C  =  O      +      H—  CH2—  CHO    -  >     CH3—  C—  CH2—  CHO 

Acetaldehyde 

OH 

Aldol 

Now  aldol  readily  loses  water  yielding  an  unsaturated  aldehyde  just 
as  ethyl  alcohol  by  loss  of  water  yields  ethylene  (p.  154). 


CH3—  CH—  CH—  CHO         ___:        CH3—  CH  =  CH—  CHO 

otonic  Ald 
A2-Buten 


Crotonic  Aldehyde 
-al 


(OH    H) 

Aldol 

In  this  reaction  which  may  apparently  be  brought  about  in  one  step, 
though  aldol  is  undoubtedly  an  intermediate  product  even  when  it  is 


170  ORGANIC  CHEMISTRY 

not  isolated,  it  has  been  definitely  shown  that  the  two  atoms  of  hydrogen 
which  go  to  make  up  the  molecule  of  water  which  is  lost  both  come 
from  the  methyl  group  of  the  second  acetaldehyde  molecule.  This  estab- 
lishes the  double  bond  in  crotonic  aldehyde  as  between  the  second  and 
third  carbon  groups  as  in  A£-buten-al.  The  condensation  of  acetalde- 
hyde to  crotonic  aldehyde  as  one  reaction  may  be  written  therefore, 


CH3—  CH=(O  +H2)  =  CH—  CHO  CH3—  CH  =  CH—  CHO 

Acetaldehyde  Crotonic  Aldehyde 

Other  reactions  support  this  constitution  for  crotonic  aldehyde. 

Higher  Ethene  Aldehydes 

Geranial.  —  Corresponding  to  the  higher  ethene  alcohol  geraniol 
(p.  167)  is  the  aldehyde  derived  from  it  and  known  as  geranial.  It 
has  the  constitution 

CH3—  C  =  CH—  CH2—  CH2—  C  =  CH—  CHO 

Geranial 
CH3  CH3 

This  compound  and  a  related  one  known  as  citronellal  belong  with 
geraniol  in  the  class  of  terpenes  and  will  be  considered  in  Part  II. 

E.  UNSATURATED  ACIDS 

Just  as  the  saturated  primary  alcohols  on  oxidation  yield  first 
aldehydes  and  then  acids  so  the  ethylene  unsaturated  primary  alcohols 
yield  first  the  unsaturated  aldehydes,  just  considered,  and  these  on 
further  oxidation  yield  corresponding  unsaturated  acids, 

CH2  =  CH—  CH2OH  -  >CH2  =  CH—  CHO  -  >CH2  =  CH—  COOH 

Allyl  alcohol  Acrylic  aldehyde  Acrylic  acid 

Ai-Propenol-3  Propen-al  Propenoic  acid 

CH3—  CH  =  CH—  CH2OH  -  »CH3—  CH  =  CH—  CHO  -  > 

A2-Buten-ol-i  Crotonic  aldehyde 

Ao-Buten-al 

CH3—  CH  =  CH—  COOH 

Crotonic  acid 
Az-Butenoic  acid 

Synthesis.  —  The  synthetical  preparation  of  these  ethylene  un- 
saturated acids  may  be  accomplished  by  the  same  general  reactions 
as  those  used  in  the  preparation  of  the  saturated  acids. 

(i)  By  the  oxidation  of  the  unsaturated  aldehyde;  as  in  the  reactions 
above. 


UNSATURATED   ALCOHOLS,    ALDEHYDES   AND    ACIDS  171 

(2)  From  the  unsaturated  alcohols,  or  the  halogen  substitution  products, 
by  conversion,  first,  into  the  corresponding   cyanide,  or  acid  nitrile, 
and  the  hydrolysis  of  this  to  the  acid  containing  one  more  carbon  than 
the  original  alcohol  or  halogen  compound. 

CH2  =  CH— CH2— OH        >        CH2  =  CH— CH2I        > 

Allyl  alcohol  Allyl  iodide 

CH2  =  CH— CH2— CN        >        CH3— CH  =  CH— COOH 

Crotonic  nitrile  Crotonic  acid 

Allyl  cyanide  A2-Butenoic  acid 

In  this  series  of  reactions  there  occurs  a  shifting  of  the  double  bond  from 
the  first  to  the  second  carbon  atom  either  in  the  allyl  cyanide  or  when 
this  is  hydrolized  to  the  acid  for  the  acid  obtained  is  crotonic  acid 
which  as  we  shall  see  has  the  constitution  of  A2-butenoic  acid. 

(3)  From   the   corresponding  saturated  acid,  which  contains  in  the 
second  carbon  group  from  the  carboxyl,  i.e.,  the  beta  position,  either 
a  substituted  halogen  atom,  or,  a  hydroxyl  group. 

TTT 

CH3— CHI— CH2— COOH    _ __,    CH3— CH  =  CH— COOH 

0-Iodo  butyric  acid  Crotonic  acid 

CH3— CH(OH)— CH2— COOH 

0-Hydroxy  butyric  acid 

CH3— CH  =  CH— COOH 

These  syntheses  are  similar  to  those  of  ethylene  from  iodo  ethane  by  the 
loss  of  hydrogen  iodide  and  from  ethyl  alcohol  by  the  loss  of  water. 

TTT  TT f\ TT 

CH3— CH2I        __;       CH2  =  CH2        T— 1        CH3— CH2— OH 

Iodo  ethane  Ethene  Ethyl  alcohol 

They  are  also  similar  to  the  one  referred  to  in  the  formation  of  crotonic 
aldehyde  from  /3-hydroxy  butenal. 

(4)  Another  general  method  of  synthesis  of  unsaturated  acids  from 
saturated  compounds  involves  this  same  reaction  as  a  second  step. 

Perkin-Fittig  Synthesis. — The  first  step  in  the  synthesis  is  analog- 
ous to  the  aldol  condensation.  It  consists  in  the  addition  of  a  sodium 
salt  of  an  acid,  usually  acetic  acid,  to  a  saturated  aldehyde,  whereby 
condensation  is  effected  and  a  beta-hydroxy  acid  is  formed.  The  beta- 


!  7  2  ORGANIC  CHEMISTRY 

hydroxy  acid  is  then  converted  into  the  unsaturated  acid  in  the  same 

way  as  in  (3). 

CH3— CHO  +  HCH2— COONa  — > 

Acetaldehyde  Sodium  acetate 

CH3— CH(OH)— CH(H)— COONa     '^^^ 

0-Hydroxy  butyric  acid 

Na  salt) 

CH3— CH  =  CH— COONa 

Crotonic  acid 

(Na  salt) 

This  is  the  simplest  case  of  the  reaction  but  it  has  been  mostly  used  in 
the  synthesis  of  higher  members  of  the  unsaturated  acid  series,  e.g., 
the  nine  carbon  acid,  nonylenic  acid,  which  is  prepared  from  the  seven 
carbon  aldehyde  known  as  oenanthylic  aldehyde,  or  oenanthol,  obtained 
from  castor  oil.  Even  more  important  than  its  application  in  the  syn- 
thesis of  higher  acids  of  the  ethylene  series  is  the  use  of  the  reaction 
in  the  synthesis  of  aromatic  unsaturated  acids  derived  from  benzene  and 
containing  an  unsaturated  side  chain  (see  cinnamic  acid,  Part  II). 
The  reaction  is  known  as  the  Perkin  Synthesis  or  as  the  Perkin-Fittig 
Synthesis  from  the  men  who  suggested  and  explained  it. 

Acrylic  Acid    CH2  =  CH— COOH    Propenoic  Acid 

The  first  member  of  the  ethylene  series  of  acids,  viz.,  propen-oic 
acid,  or  as  it  is  commonly  known,  acrylic  acid,  is  a  sharp  smelling  liquid 
which  boils  at  140°  and  melts  at  7°.  It  readily  forms  addition  products. 
With  hydrogen  it  yields  propionic  acid;  with  hydrogen  iodide,  0-iodo 
propionic  acid  and  with  water,  /3-hydroxy  propionic  acid.  This  last 
acid,  which  we  will  consider  later  (p.  245),  because  of  this  relation  to 
acrylic  acid,  is  also  known  as  hydracrylic  acid.  From  these  compounds 
just  mentioned  acrylic  acid  may  be  formed  by  the  loss  of  the  same 
elements. 

+  H2 
CH2  =  CH— COOH        " !        CH3— CH2— COOH 

Acrylic  Acid  TT  Propionic  acid 

+  HI 
CH2  =  CH— COOH        HI^.        CH2I— CH2— COOH 

TTT  /3-Iodo  propionic  acid 

+  H— OH 
CH2  =  CH— COOH        TZZ !        CH2(OH)— CH2— COOH 

H— OH          0-Hydroxy  propionic  acid 


UNSATURATED    ALCOHOLS,    ALDEHYDES    AND   ACIDS  173 

Other  methods  of  preparing  acrylic  acid  are  by  the  oxidation  of  the 
corresponding   unsaturated   alcohol   or  aldehyde,   viz.,  allyl  alcohol, 
CH2  =  CH—  CH2—  OH,   and  acrylic  aldehyde,   CH2  =  CH—  CHO. 

Crotonic  Acid     CH3—  CH  =  CH—  COOH     A2-Butenoic  Acid 

The  second  acid  of  the  ethylene  unsaturated  series,  viz.,  one  con- 
taining four  carbon  atoms,  therefore  a  derivative  of  butene  and  sys- 
tematically named  butenoic  acid,  is  a  naturally  occurring  substance 
known  as  crotonic  acid.  We  have  mentioned  the  fact  that  the  exist- 
ence of  the  double  bond,  in  compounds  containing  more  than  three 
carbon  groups  in  the  chain,  increases  the  possibility  of  isomerism  be- 
cause of  the  different  position  which  the  double  bond  may  occupy. 
Butenoic  acid,  as  it  contains  one  double  bond,  or  ethene  group,  may, 
according  to  the  different  position  which  the  double  bond  may  occupy, 
and  also  because  of  the  different  position  which  the  methyl  group  may 
occupy,  exist  in  all  of  the  following  forms: 

(A)  CH3—  CH  =  CH—  COOH  A2-Butenoic  acid 

(B)  CH2  =  C(CH3)—  COOH  2  -Methyl  propenoic  acid 

(C)  CH2  =  CH—  CH2—  COOH  Ar-Butenoic  acid 

Also,  a  fourth  possibility  exists  for  an  acid  of  the  composition,  C3H5— 
COOH,  which,  however,  has  an  entirely  different  constitution,  viz., 


2v 

)CH—  COOH 
CR/  CH/ 

Tri-methylene  Tri-methylene 

carbozylic  acid 

Such  an  acid  is  known  but  it  is  not  an  unsaturated  compound.  It  is 
what  is  termed  a  cyclic  compound  derived  from  a  hydrocarbon  known  as 
tri-methylene,  and  also  as  cyclo  propane  (Pt.  II).  The  acid  is  thus 
known  as  tri-methylene  carboxylic  acid  and  also  as  cyclo  propanoic 
acid. 

Let  us  consider  then  only  those  acids  of  the  composition  C3H5  — 
COOH  which  contain  a  double  bond  or  ethene  group  and  the  possible 
constitutions  of  which  we  have  represented  above  by  the  formulas  (A), 


174  ORGANIC  CHEMISTRY 

(B),  and  (C).  Now  the  fact  is  that  not  three  acids  only  but  four  are 
known  which  correspond  to  the  three  possible  constitutions.  How 
then  are  these  facts  harmonized  ?  The  four  known  acids  are 

m.p.  b.p. 

Crotonic  acid,  a  solid          71°  180° 

Iso-cro tonic  acid,  a  liquid        15°  172° 

Methyl  acrylic  acid,        a  solid          16°  160° 

Vinyl  acetic  acid,  a  liquid  168° 


alpha-M.  ethyl  Acrylic  Acid.  —  The  third  acid  methyl  acrylic  acid 
may  be  synthesized  from  a-brom  iso-butyric  acid,  or  2-brom  2-methyl 
propanoic  acid,  by  loss  of  hydrobromic  acid  with  potassium  hydroxide 
just  as  acrylic  acid  is  made  from  #-brom  propionic  acid. 

CH3  CH3 


CH2—  C—  COOH   _  T  CH2  =  C—  COOH 

a-Methyl  acrylic  acid 

(H        Br) 

a-Brom  iso-butyric  acid 

This  synthesis  proves  it  to  be  the  a//>^a-methyl  acrylic  acid  correspond- 
ing to  formula  (B).    That  is,  2-methyl  propanoic  acid. 

Vinyl  Acetic  Acid.  —  Vinyl  acetic  acid  may  be  synthesized  from  allyl 
bromide  by  means  of  the  Grignard  reaction  which  introduces  the  car- 
boxyl  group  in  place  of  the  halogen.  This  proves  the  constitution  to  be 
that  of  Ai-butenoic  acid. 

CH2  =  CH—  CH2—  Br  +  Mg    --  >     CH2  =  CH—  CH2—  MgBr 

Allyl  bromide  Magnesium  allyl  bromide 

CH2  =  CH—  CH2—  MgBr  +  CO2  ---  >  CH2  =  CH—  CH2—  COOMgBr 

CH2  =  CH—  CH2—  COO  (MgBr  +  HO)—  H       -» 

CH2  =  CH—  CH2—  COOH  +  Mg(OH)Br 

Vinyl  acetic  acid 
Ai-Butenoic  acid 

Crotonic  and  Iso-crotonic  Acids.  —  We  have  then  for  the  two  cro- 
tonic  acids  only  one  possible  constitution  remaining  and  their  synthesis 
proves  that  both  of  these  acids  do  in  fact  have  the  same  structural  con- 
stitution, viz.,  that  of  0-methyl  acrylic  acid  or  A2-butenoic  acid. 


UNSATURATED    ALCOHOLS,    ALDEHYDES    AND    ACIDS  175 

Crotonic  Acid  from  Crotonic  Aldehyde. — We  have  previously  shown 
(p.  169),  that  crotonic  aldehyde  is  A2-butenal  because  of  its  synthesis 
by  the  aldol  condensation  of  acetaldehyde.  On  simple  oxidation  cro- 
tonic aldehyde  yields  crotonic  acid  which  must  therefore  have  the 
constitution  of  A2-butenoic  acid, 

+  0 
CH3— CH(0  +  H2)CH— CHO >    CH3— CH  =  CH— CHO  -  — > 

Acetaldehyde  Crotonic  aldehyde 

Ai-Butenal 

CH3— CH  =  CH— COOH 

Crotonic  acid 
Aj-Butenoic  acid 

From  Acetaldehyde  and  Malonic  Acid. — Another  synthesis  proves 
the  constitution  of  crotonic  acid  as  A2-butenoic  acid.  A  di-basic  acid 
known  as  malonic  acid  has  the  constitution  of  di-carboxy  methane, 
HOOC— CH2— COOH.  When  this  acid  is  heated  with  acetaldehyde 
(paraldehyde)  and  glacial  acetic  acid  condensation  occurs  as  in  the  syn- 
thesis of  crotonic  aldehyde  and  in  the  Perkin-Fittig  synthesis  (p.  172). 
A  dibasic  acid  is  obtained  which  loses  carbon  dioxide  and  yields  a 
mono-basic  acid  which  is  crotonic  acid. 


CH3— CH(0  +  H2)C— COOH     -H2O 

Acetaldehyde  > 

COOH 

Malonic  acid 

f/") 

CH3— CH  =c— COOH    _±;2 

I  CH3— CH  =  CH— COOH 

(COO)H  Crotonic  acid 

Now  iso-crotonic  acid  is  readily  transformed  into  crotonic  acid  by 
simply  heating  to  170°  and. crotonic  acid  may  likewise  be  converted 
into  iso-crotonic  acid.  Also  each  of  them  by  the  addition  of  hydrogen 
iodide  is  converted  into  the  same  saturated  compound,  viz.,  /3-iodo 
butyric  acid. 

CH3— CH  =  CH— COOH '+  HI >     CH3— CHI— CH2— COOH 

Crotonic  acid  or  /?-Iodo  butyric  acid 

Iso-crotonic  acid 

Other  reactions  support  the  view  that  these  two  crotonic  acids,  which 
differ  sharply  in  physical  properties  but  closely  resemble  each  other  in 


176  ORGANIC  CHEMISTRY 

their  chemical  properties,  being  formed  by  the  same  reactions,  con- 
vertible into  the  same  products  and  easily  transformed  into  each  other, 
are  in  fact  of  identical  structure,  viz.,  that  of  /3-methyl  acrylic  acid  or 
A2-butenoic*acid.  We  have  then  the  following  facts  established  as 
to  the  structural  constitution  of  the  four  acids  we  are  discussing. 

Crotonic  acid 

and  CH  3-r-CH  =  CH— COOH  /3-Methyl  acrylic  acid 

Iso-crotonic  acid  A2-Butenoic  acid 

Methyl  acrylic  acid    CH2  =  C(CH3)— COOHa-Methyl  acrylic  acid 

2 -Methyl  propenoic  acid 
Vinyl  acetic  acid         CH2  =  CH— CH2— COOH  Ai-Butenoic  acid 

Having,  then,  two  different  acids,  of  the  same  constitution,  it  is  neces- 
sary to  explain  their  existence  and  their  difference  by  some  theory  of 
isomerism.  This  brings  us  to  the  consideration  of  a  new  kind  of  space- 
isomerism.  In  connection  with  active  amyl  alcohol  or  2-methyl 
butanol-i,  we  discussed  the  van't  Hoff-LeBel  theory  of  the  asymmetric 
carbon  atom,  by  which  the  existence  of  three  stereoisomeric  compounds 
may  be  explained.  The  compounds  all  have  the  same  structure  but 
differ  in  the  arrangement  of  the  atoms  and  groups  in  space  around  a 
central  asymmetric  carbon  atom.  This  carbon  atom,  because  of  its 
union  to  four  different  atoms  or  groups,  takes  on  the  property  of  asym- 
metry and  forms  right-  and  left-handed  compounds.  According  to 
this  theory,  carbon  is  represented  as  a  tetravalent  element  situated  at 
the  center  of  a  regular  tetrahedron,  with  the  lines  representing  its  union 
with  other  elements  directed  toward  the  apexes  of  the  tetrahedron, 
as  shown  in  Fig.  i,  p.  90. 

In  the  case  of  tartaric  acid,  which  we  shall  study  later,  we  have  to 
consider  two  such  carbon  atoms  directly  united  to  each  other  by  one 
of  the  bonds,  and  we  shall  find  that  the  theory  applies  as  truly  here  as 
in  the  first  case  given  of  the  active  amyl  alcohols. 

Geometric  Isomerism.— The  theory  was  applied  by  van't  Hoff  and 
Wislicenus  to  the  present  case  of  the  isomeric  crotonic  acids,  and  other 
compounds  of  similar  character,  viz.,  maleic  acid  and  fumaric  acid 
(p.  290).  If  two  carbon  atoms,  instead  of  being  linked  by  one  bond, 
become  directly  linked  by  a  double  bond,  as  in  the  case  of  crotonic  acid 
and  iso-crotonic  acid,  the  relation  of  the  two  carbon  atoms,  and  of  the 
two  groups  containing  them,  becomes  fixed  in  space,  because  the  double 


UNSATURATED    ALCOHOLS,    ALDEHYDES   AND   ACIDS 


177 


bond  prevents  rotation  of  these  carbon  groups.     We  may  write  the 
formulas  on  a  plane  surface  as  follows: 

(A)  (B) 

H— C— CH3  CH3— C— H 

CH3— CH  =  CH— COOHor          ||                and  || 

H— C— COOH  H— C— COOH 

Crotonic  and  Iso-crotonic  acids  or  /3-Methyl  acrylic  acid 

If  we  represent  the  formulas  by  the  tetrahedral  figures  we  have  the 
following: 

' 


OH 


Crotonic  actd 
cts  form 

H-OCH, 

II 
H-C-COOH 


IjSo-crotonic  acid 
irarvs    form 

H3c-C-H 

II 
H-C-COOH 


PIG.  3. 


As  this  position  is  fixed  in  space  isomeric  compounds  are  possible  in 
which  the  position  of  two  of  the  elements  or  groups  linked  to  the 
doubly  bound  carbon  atoms  are  reversed,  as  in  (A)  and  (B)  above. 
Two  stereo-is omeric  compounds  should  therefore  be  possible  according 
to  such  a  space  arrangement  and  the  two  isomeric  crotonic  acids 
may  thus  be  explained.  This  kind  of  stereo-isomerism  is  termed 
geometric  isomerism.  Without  taking  up  in  detail  the  proofs  as  to 
which  of  the  two  stereo-chemical  formulas  applies  to  each  of  the  two 
crotonic  acids,  we  may  simply  state  the  fact,  that  the  properties  of 
the  solid  or  ordinary  crotonic  acid  prove  that  it  must  be  represented 
by  formula  (A),  above,  in  which  the  methyl  and  carboxyl  groups  are 
12 


178  ORGANIC  CHEMISTRY 

both  on  the  same  side.  Because  these  two  groups  are  on  the  same 
side  this  particular  formula  is  known  as  the  cis  form.  The  other 
formula,  in  which  these  two  groups  are  on  opposite  sides  represents, 
similarly,  the  trans  form.  The  iso-crotonic  acid  is  represented,  there- 
fore, by  the  trans  formula.  The  formulas,  then,  for  the  two  struc- 
turally identical  but  stereo-isomeric  0-methyl  acrylic  acids  or  crotonic 
acids,  are, 

H— C— CH3  H—  C— CH3 

II  II 

H— C— COOH  HOOC— C— H 

cis  form  trans  form 

Crotonic  acid  Iso-crotonic  acid 

Crotonic  acid,  the  solid,  crystallizes  from  hot  water  in  fine  needles 
which  melt  at  71°  to  72°  and  boil  at  180°  to  185°.  It  is  soluble  in  12 
parts  of  water  at  15°.  Iso-crotonic  acid,  the  liquid,  is  a  colorless  oily 
liquid  with  a  strong  odor  resembling  butyric  acid.  It  boils  at  172° 
and  melts  at  about  15°.  It  mixes  with  water  in  all  proportions. 

Tiglic  Acid  and  Angelic  Acid    CH3— CH  =  C(CH3)— COOH 

Two  pairs  of  higher  acids  of  this  series  are  known,  the  members  of 
each  pair  being  related  to  each  other  as  are  crotonic  and  iso-crotonic 
acids.  The  first  two  are  known  as  tiglic  acid  and  angelic  acid  and 
they  have  been  proven  to  be  the  alpha-methyl  substitution  products  of 
the  two  crotonic  acids.  Tiglic  acid  is  a-methyl  crotonic  acid  and  is 
therefore  the  cis  form.  Angelic  acid  is  a-methyl  iso-crotonic  acid  and 
is  the  trans  form. 

Tiglic  acid  H— C— CH8 

a-Methyl  crotonic  acid 

CH3— C— COOH 
Angelic  acid  CH3— C— H 

II 
a-Methyl  iso-crotonic  acid        CH3—  C-— COOH 

Oleic  Acid  and  Elaidic  Acid    CHs— (CH2)7— CH  =  CH—  (CH2)r- COOH 

The  second  pair  of  higher  unsaturated  acids  exhibiting  geometric 
isomerism  is  oleic  acid  and  elaidic  acid.  Oleic  acid  is  of  especial  im- 
portance because,  as  a  glycerol  ester,  it  occurs  very  commonly  as  a 
constituent  of  many  animal  and  vegetable  fats  and  oils.  While  most 


UNSATURATED  ALCOHOLS,  ALDEHYDES  AND  ACIDS     179 

of  the  acids  which  occur  as  esters  in  fats  and  oils  are  members  of  the 
saturated  series  a  few  unsaturated  acids  are  also  found.  Oleic  acid 
the  most  important  one  belongs  to  the  ethene  series  and  is  the  eighteen 
carbon  member,  i.e.  Ci7H33 — COOH,  derived  from  the  hydrocarbon 
CisHse.  Elaidic  acid  has  the  same  composition  and  has  been  shown  to 
be  the  geometric  isomer  of  oleic  acid. 

One  Double  Bond. — That  oleic  acid  and  elaidic  acid  are  normal 
or  straight  chain  compounds  each  containing  one  double  bond  is 
proven  by  the  addition  products  which  they  form  with  hydrogen,  in 
the  presence  of  nickel  catalyser,  with  bromine,  hydrobromic  acid  and 
water.  With  these  reagents  they  each  yield  stearic  acid,  di-brom 
stearic  acid,  mono-brom  stearic  acid  and  mono-hydroxy  stearic  acid 
respectively,  adding  in  each  case  two  hydrogen  atoms  or  the  equivalent. 
Also  mild  oxidation  converts  them  each  into  di-hydroxy  stearic  acid. 
As  stearic  acid  has  been  proven  to  be  the  normal  eighteen  carbon  satu- 
rated mono-basic  acid,  these  reactions  prove  that  oleic  acid  and  elaidic 
acid  both  have  the  structure  of  a  normal  eighteen  carbon  unsaturated 
acid  containing  one  double  bond. 

Position  of  Double  Bond. — The  position  of  the  double  bond  and  the 
full  constitution  of  oleic  acid  and  elaidic  acid  has  been  established  by 
means  of  the  products  obtained  by  careful  oxidation.  It  has  been 
shown  that  when  compounds  containing  a  double  bond  are  thus  oxidized 
the  effect  is  to  split  the  compound  at  the  double  bond  with  the  oxida- 
tion of  each  doubly  linked  carbon  group  to  carboxyl.  Now  both  oleic 
acid  and  elaidic  acid  on  oxidation  yield  two  acids,  each  containing 
nine  carbon  atoms.  One  is  a  mono-basic  acid  known  as  pelargonic 
acid,  C8Hi7 — COOH;  and  the  other  is  a  di-basic  acid,  azelaic  acid, 
HOOC— C7H14— COOH.  The  reaction  is 

CH3— (CH2)7— CH  =  CH— (CH2)7— COOH      +_£ 

Oleic  acid  or  Elaidic  acid 

CH3—  (CH2)7— COOH  +  HOOC— (CH2)  7— COOH 

Pelargonic  acid  Azelaic  acid 

This  proves  that  in  both  of  these  acids  the  double  bond  is  between  car- 
bon atoms  nine  and  ten  or  in  the  middle  of  the  straight  chain  of  eighteen 
carbon  atoms. 

Conversion  of  Oleic  into  Elaidic  Acid. — Furthermore,  oleic  acid, 
a  liquid  is  easily  converted,  by  means  of  a  small  amount  of  nitrous  acid 
into  white  solid  elaidic  acid.  This  reaction  is  of  the  nature  of  other 


180  ORGANIC  CHEMISTRY 

reactions  by  which  geometric  isomers  are  transformed  into  each  other. 
AH  of  these  facts  go  to  prove  that  oleic  acid  and  elaidic  acid  are  geo- 
metric isomers  exactly  analogous  to  crotonic  acid  and  iso-crotonic  acid. 
The  two  acids  may  thus  be  represented  by  the  following  formulas 
though  it  has  not  been  fully  established  as  to  which  one  has  the  cis 
and  which  the  trans  form. 

CH3— (CH2)  7C— H  H—  C—  (CHj)  7— CH3 

II  II 

H— C— (CH2)  7— COOH         H— C— (CH2)  7— COOH 

Oleic  acid  (?)  ,     Elaidic  acid  (?) 

(trans)  (cis) 

Iso-oleic  Acid. — It  should  also  be  mentioned  that  a  third  isomeric 
ethene  unsaturated  acid  of  this  composition  is  known,  viz.,  iso-oleic 
acid.  The  isomerism  in  this  case  is  probably  structural  and  consists 
in  a  change  in  the  position  of  the  double  bond,  which  is  considered  to  be 
between  carbon  atoms  two  and  three,  viz.,  CH3 — (CH2)i4 — CH  =  CH — 
COOH.  Oleic  acid  was  discovered  by  Chevreul  in  1846.  It  is  a  clear 
colorless  oily  liquid  without  odor  or  taste  and  is  easily  oxidized  in  the 
air.  On  cooling  it  solidifies  to  a  white  crystalline  mass  melting  at  14°. 
Under  a  pressure  of  10  m.m.  it  boils  at  223°  but  distills  without  de- 
composition at  250°  with  superheated  steam.  It  differs  from  the  higher 
saturated  acids  in  yielding  a  lead  salt  which  is  easily  soluble  in  ether, 
thus  affording  a  method  for  its  separation  and  isolation.  Elaidic  acid 
is  a  solid  melting  at  about  45°. 

As  was  stated,  oleic  acid  occurs  as  an  ester  in  many  common  fats 
and  oils.  In  common  with  other  unsaturated  acids  it  possesses  the 
characteristic  property  of  forming  addition  products  with  the  halogens 
or  halogen  acids.  This  property  it  imparts  to  the  fats  and  oils  in  which 
it  is  present  as  an  ester  giving  another  important  method  for  the  analysis 
of  these  substances.  This  and  the  other  properties  and  reactions  of 
oleic  acid  which  are  important  in  connection  with  the  analysis  of  fats 
and  oils  will  be  considered  again  when  we  study  these  substances. 

Hypogaeic  Acid    C16H29— COOH 

The  acid  next  lower  than  oleic  acid  should  be  mentioned.  This 
is  hypogaeic  acid,  the  ethene  unsaturated  acid  containing  sixteen 
carbon  atoms,  Ci5H29 — COOH.  Together  with  arachidic  acid  which 
is  the  twenty  carbon  saturated  acid,  Ci9H39 — COOH  it  is  present  as 
an  ester  in  peanut  oil.  The  two  acids  receive  their  names  from  the 


UNSATURATED    ALCOHOLS,    ALDEHYDES    AND    ACIDS  l8l 

botanical  name  for  the  peanut  plant,  Arachis  hypogaea.     They  were 
both  discovered  by  Goessmann  in  1854-1855. 

Linoleic  and  Linolenic  Acids 

We  have  referred  to  the  fact  (p.  162),  that  compounds  of  greater 
unsaturation  than  the  ethine  series  are  known  in  which  the  greater 
unsaturation  is  due  to  the  presence  in  the  molecule  of  more  than  one 
double  or  triple  bond.  From  fats  and  oils  three  acids  have  been  iso- 
lated which  are  of  this  character.  They  are  linoleic  acid,  CnHsi — 
COOH  derived  from  the  hydrocarbon  Ci8H34  or  CnH2r!_2  and  linolenic 
acid  and  iso-linolenic  acid  both  of  which  have  the  composition 
Ci7-H29 — COOH  derived  from  the  hydrocarbon  Ci8H32  or  CnH2ri_4. 
The  first  of  these  acids  linoleic  acid  has  been  shown  to  contain  two  double 
bonds,  while  the  last  two  linolenic  acid  and  isolinolenic  acid  each  contain 
three  double  bonds.  The  isomerism  of  the  last  two  being  due  to  the 
different  positions  which  the  three  double  bonds  occupy.  All  of  these 
acids  possess  in  a  marked  degree  the  properties  of  unsaturation  which 
properties  they  confer  upon  the  fats  and  oils  in  which  they  occur  as 
esters.  They  are  all  found  especially  in  certain  oils,  e.g.,  linseed  oil 
possessing  properties  characterizing  them  as  drying  oils,  due  to  their 
easy  oxidation.  These  properties  and  facts  in  connection  with  them 
will  be  discussed  under  fats  and  oils. 

Propiolic  Acid    CH=C— COOH    Propinoic  Acid 

By  the  oxidation  of  propargyl  alcohol,  propinol,  CH  =  C — CH2OH 
(p.  167),  an  acid  is  obtained  having  the  constitution  CH  =  C — COOH 
and  known  as  propiolic  acid  or  propinoic  acid  and  also  as  acetylene 
carboxylic  acid.  This  is  the  simplest  acid  of  the  ethine  series  and  the 
only  one  we  shall  mention.  Derivatives  of  it  are  of  importance  in  the 
benzene  series  in  Part  II  as  will  be  shown  later. 


C.  POLY-SUBSTITUTION  PRODUCTS 
VI.  POLY-HALIDES,  -CYANIDES  AND  -AMINES 

The  compounds  which  we  have  considered  thus  far  are  the  hydro- 
carbons, both  saturated  and  unsaturated  and  the  mono-substitution 
products  derived  from  them.  We  have  now  to  consider  the  compounds 
wh  ch  result  from  the  substitution  into  the  hydrocarbon  chain  of  more 
than  one  element  or  group.  These  are  known  as  poly-substitution  prod- 
ucts from  the  Greek  word  poly  meaning  many.  These  compounds  are 
of  two  kinds;  first,  those  in  which  the  substituting  elements  or  groups 
are  the  same,  termed  poly  compounds;  and  second,  those  in  which  the 
substituting  elements  or  groups  are  of  different  character,  termed 
mixed  compounds.  These  last  may  be,  for  example,  mixed  halides  and 
alcohols,  mixed  alcohols  and  acids,  mixed  amines  and  acids,  etc.  The 
poly  compounds  of  the  first  class  will  include  the  following  groups: 

Poly-halides 

Poly-amines 

Poly-cyanides  and  iso-cyanides 

Poly-hydroxy  compounds  or  poly-acid  alcohols 

Poly-aldehydes 

Poly-carboxy  acids  or  poly-basic  acids 

A.  POLY-HALIDES 
I.  POLY-HALOGEN  METHANES 

At  the  very  beginning  of  our  study  we  stated  that  when  methane 
gas  is  acted  upon  by  chlorine  in  the  sunlight  a  mixture  of  four  products 
is  obtained  resulting  from  the  substitution  of  one,  two,  three  or  four 
chlorine  atoms  for  an  equivalent  number  of  hydrogen  atoms  in  the 
methane  molecules.  These  four  compounds  are  represented  by  the 
following  formulas: 

H  H  Cl  Cl  Cl 

I  III 

H— C— H        H— C— Cl        H— C— Cl        H— C— Cl        Cl— C— Cl 

I  I  I  I 

H  H  H  Cl  Cl 

Methane  Mono-chlor  Di-chlor  Tri-chlor  Tetra-chlor 

methane  methane  methane  methane 

182 


POLY-HALIDES  -  183 

The  three  poly-chlorine  substitution  products  of  methane,  as  repre- 
sented above,  are  all  known,  but  only  two  of  them  are  of  sufficient 
importance  to  be  considered  in  detail. 

Chloroform    CHC13    Tri-chlor  Methane 

The  tri-chlorine  substitution  product  of  methane  is  the  common 
and  very  important  anesthetic  chloroform.  It  may  be  made  by  the 
method  referred  to,  viz.,  by  the  direct  chlorination  of  methane.  This 
method  is  not,  however,  a  practical  one.  The  industrial  preparation 
is  from  alcohol  or  acetone,  by  treatment  with  chlorine  and  an  alkali. 
In  the  reaction  with  alcohol  the  chlorine  acts,  first,  as  an  oxidizing 
agent,  oxidizing  the  alcohol  to  aldehyde.  The  chlorine  then  acts  as  a 
substituting  agent  forming  a  tri-chlorine  substitution  product  of  the 
aldehyde.  This  tri-chlor  aldehyde  is  then  decomposed  by  the  alkali 
and  chloroform  results.  The  steps  in  this  reaction  have  been  definitely 
proven,  as  follows: 


CH3-CH2-OH  +  0          2_' 

Ethyl  alcohol 

CH3-CHO  +  3C12         -  >         CC13-CHO 

Acet-aldehyde  Tri-chlor  aldehyde 

CC13-(CHO     +      KO)-H    -  >    CC13H      +      H  -  COOK 

Tri-chlor  aldehyde  Chloroform  Potassium 

Tri-chlor  methane  formate 

In  practice,  the  chlorination  is  effected,  not  by  the  use  of  free 
chlorine,  as  such,  but  by  the  use  of  bleaching  powder,  calcium  hypo- 
chlorite.  The  preparation  from  acetone  is  by  a  similar  chlorination. 
In  the  reaction  which  takes  place,  one  of  the  methyl  groups  is  substi- 
tuted just  as  in  the  case  of  aldehyde,  and  then  a  similar  decomposition 
by  means  of  the  alkali  takes  place. 

->    CC13-  (C  =  0  +  KO)-H 


CH3  CH3 

Acetone  Tri-chlor  acetone 

CC13H    +    CH3  -  COOK 

Chloroform  Potassium  acetate 

The  removal  of  the  carbonyl  group  by  alkalies,  producing  formic  acid, 
in  one  case,  and  the  methyl  homologue,  acetic  acid,  in  the  other,  is 


184  ORGANIC  CHEMISTRY 

analogous  to  the  preparation  of  formic  acid  from  carbon  monoxide  and 
potassium  hydroxide. 

CO  +  KO-H        >        H  -  COOK 

Potassium  formate 

In  the  industrial  application  of  this  reaction  in  the  preparation  of 
chloroform,  a  mixture  of  bleaching  powder  and  dilute  alcohol  (85- 
90  per  cent.)  or  acetone,  is  heated  with  steam,  until  action  begins.  The 
steam  is  then  cut  off  as  the  reaction  usually  continues  without  additional 
heat,  oftentimes  becoming  too  violent.  When  the  reaction  quiets 
down  steam  is  again  admitted  and  distillation  is  begun.  The  dis- 
tillate which  passes  over  consists  of  two  layers,  a  lower  heavier  layer  of 
chloroform  and  an  upper  lighter  layer  of  dilute  alcohol  or  acetone.  The 
chloroform  is  separated  from  the  lighter  liquids  and  is  washed  with 
acid  (sulphuric)  and  then  with  water.  It  is  then  dried  with  calcium 
chloride  and  redistilled  as  pure  chloroform.  Chloroform  is  a  heavy, 
colorless,  mobile  liquid  with  a  sweet  suffocating  odor.  It  melts  at 
—  70°  and  boils  at  61°.  It  has  a  specific  gravity,  at  15°,  of  1.49.  It  is 
only  slightly  soluble  in  water  and  does  not  mix  with  it.  It  is  non- 
inflammable,  but  imparts  a  green  color  to  a  colorless  flame,  due  to  the 
chlorine  present.  It  was  discovered  in  1831  by  Liebig  and  Soubeiran. 
Its  action  and  use  as  an  anesthetic  was  discovered  in  1848  by  an  Eng- 
lishman, Simpson.  As  an  anesthetic  it  is  used,  not  in  a  pure  state,  but 
with  about  i  per  cent,  of  alcohol  mixed  with  it.  With  this  amount  of 
alcohol  present  the  decomposition  of  the  chloroform,  by  air  and  light, 
into  chlorine,  hydrochloric  acid,  and  phosgene  .gas  (COC12),  is  hind- 
ered. This  decomposition  shows  the  ease  with  which  the  chlorine  is 
removed  from  the  compound. 

CHC13  +    O  — >          COC12  +  HC1 

CHC13  +  2O2  -»        2COC12  +  C12  +  H2O 

Chloroform  Phosgene 

Chloroform  Reactions. — This  ready  giving  up  of  its  chlorine  is  also 
shown  by  the  reactions  of  chloroform  with  alkalies,  with  ammonia  and 
with  amines.  With  alkalies  chloroform  yields  salts  of  formic  acid. 
This  reaction  consists  in  a  replacement  of  all  of  the  chlorine  by  hydroxyl 
yielding  a  tri-hydroxy  methane.  As  we  have  previously  discussed, 


POLY-HALIDES  185 

when  more  than  one  hydroxyl  group  is  linked  to  one  carbon  atom  water 
is  always  lost. 
(Cl 

H—  C—  (Cl  +  3K)—  OH  —> 

(Cl 

Chloroform 


3KC1+H—  C—  OH        l£2_?       H—  C—  OH 

I  II 

O(H)  O 

Formic  acid 

Ortho  Formic  Acid.  —  Though  the  tri-hydroxy  methane  is  not  known 
we  have  proof  that  it  is  formed  as  the  intermediate  product  in  the 
foregoing  reaction,  because  if  we  use,  instead  of  potassium  hydroxide, 
the  analogous  ethoxy  compound,  viz.,  potassium  ethylate,  C2H5  —  OK, 
there  is  obtained  as  the  first  result  of  the  reaction  the  tri-ethyl  ester 
of  tri-hydroxy  methane,  or  as  it  is  known,  ortho-formic  acid,  according 
to  the  following  reaction  : 

(Cl  OC2H5 

I  I 

H—  C—  (Cl  +  3K)—  OC2H5  -  >  H—  C—  OC2H5  +  sKCl 

(Cl  OC2H5 

Chloroform  Tri-ethyl  ester 

of  Ortho-formic 
acid 

With  ammonia,  in  the  presence  of  alkalies,  chloroform  yields  hydrogen 
cyanide,  as  follows: 


H—  C(C13  +  H3)N    -  >    H—  CN  +  3HC1 

Chloroform  Hydrogen 

cyanide 

Hermann's  Isonitrile  Reaction.  —  If,  however,  instead  of  ammonia 
we  use  alkyl  primary  amines,  we  obtain  not  the  alkyl  cyanides  but  the 
alkyl  iso-cyanides 

'  (Cl 

H)\ 
H)—  C—  (Cl  +         )N—  R  -  >  C  =  N—  R  or  C  =  N—  R  +  3HC1 

H)' 

ui 

(primary) 


//-ti  Alkyl  amine 


Chloroform 


1  86  ORGANIC  CHEMISTRY 

In  this  reaction  the  nitrogen  changes  from  tri-valent  to  penta- 
valent,  or  according  to  the  other  view  in  regard  to  the  constitution  of 
iso-cyanides  (p.  71),  the  carbon  changes  from  tetravalent  to  bivalent. 
It  will  be  recalled  that  this  reaction  has  been  met  with  before  (p.  70), 
and  is  known,  as  Hofmann's  iso-nitrile  reaction.  It  is  a  test  for 
primary  amines  as  it  is  necessary  for  the  amine  to  have  two  hydrogen 
atoms  in  order  to  withdraw  two  chlorine  atoms  from  the  chloroform. 
The  characteristic  odor  of  the  iso-nitrile  makes  the  reaction  a  distinc- 
tive test,  for  either  a  primary  amine  or  for  chloroform. 

Bromoform    CHBr3    Tri-brom  Methane 

This  corresponding  bromine  compound  is  made  by  exactly  analo- 
gous reactions  to  the  ones  described  above  for  the  preparation  of  chloro- 
form. The  compound  is  a  liquid  possessing  anesthetic  properties 
though  only  slightly. 

lodoform    CHI3    Tri-iodo  Methane 

The  corresponding  iodine  compound  is  the  common  substance, 
iodoform.  It  possesses  both  anesthetic  and  antiseptic  properties  and 
is  a  most  important  surgical  disinfectant  in  the  case  of  wounds  or  cuts. 
It  is  solid,  crystallizing  in  beautiful  yellow  crystals.  It  is  practically 
insoluble  in  water  but  is  soluble  in  alcohol  and  ether.  It  is  prepared  by 
reactions  exactly  analogous  to  those  used  in  the  case  of  chloroform. 


CH3-CH2-OH  +  0          2_2 

Ethyl  alcohol 

CH3—  CHO  +  3I2    -  >    CI3—  CHO  +  3HI 

Acet-aldehyde  Tri-iodo 

aldehyde 

CI3—  (CHO    +    KO)—  H  (K2CO3)   -  >    CHI3    +    H—  COOK 

Tri-iodo  aldehyde  lodoform  Potassium 

formate 

lodoform  Test  for  Alcohol.  —  It  is  made,  in  practice,  by  adding  iodine 
to  an  alkaline  (KOH  or  K2CO3),  alcohol  and  water  solution.  The 
compound  has  a  characteristic,  very  penetrating  odor  which  may  be 
detected  even  though  an  exceedingly  small  amount  is  present.  On 
this  account  the  reaction  above  may  be  used  as  a  test  for  alcohol  by 
simply  adding  a  crystal  of  iodine  and  a  little  alkali  to  a  solution  con- 


POLY-HALIDES  187 

taining  alcohol  and  then  warming.  By  this  test  as  little  as  i  part 
alcohol  in  2000  parts  water  may  be  detected. 

Fluoroform    CHF3    Tri-fluor  Methane 

The  corresponding  fluorine  compound  is  also  known,  and  is  a  gas 
with  a  chloroform-like  odor. 

Carbon  Tetrachloride    CC14    Tetra-chlor  Methane 

This  is  the  only  tetra-halogen  substitution  product  of  methane  which 
will  be  mentioned.  It  is  produced  when  methane  is  chlorinated  to  its 
limit.  It  may  also  be  made  by  further  chlorination  of  chloroform. 
The  reaction  by  which  it  is  made  industrially  is,  however,  entirely 
different.  It  consists  in  chlorinating  carbon  di-sulphide  in  the  presence 
of  a  carrier  such  as  iodine.  In  this  reaction,  which  probably  takes  place 
in  several  steps,  the  two  sulphur  atoms,  in  the  carbon  di-sulphide,  are 
replaced  by  four  chlorine  atoms. 

CS2    +    3C12       — >      CC14    +    S2C12 

Tetra-chlor 
methane 

It  is  a  colorless  liquid  resembling  chloroform  in  odor.  It  is  a  good  solv- 
ent of  fats  and  is  much  used  for  this  purpose.  It  is  not  inflammable 
and  is  a  non-supporter  of  combustion,  acting  as  a  suffocating  blanket. 
This  property  makes  it  useful  as  a  non-inflammable  fat  solvent  or  clean- 
ing liquid,  and  also  as  a  fire  extinguisher  liquid.  It  undergoes  reaction 
with  alkalies  similar  to  that  of  chloroform,  and  yields  alkali  carbonates. 
With  water,  at  high  temperatures,  it  yields  phosgene,  COC12  carbonyl 
chloride. 

OK 

I 
CC14  +  6KOH        >        O  =  C        (K2CO3)  +  4KC1  +  3H2O 

Tetra-chlor  I 

methane 

OK 

Potassium  carbonate 

Cl 
CC14  +  H2O      >      O  =  C        +  2HC1 

Tetra-chlor  I 

methane 

Cl 

Phosgene 


1  88  ORGANIC  CHEMISTRY 

II.  POLY-HALOGEN  ETHANES 
Di-chlor  Ethanes 

Isomerism.  —  When  we  come  to  the  di-substitution  products  of 
ethane  we  find  two  classes  of  isomeric  compounds  as  was  discussed 
briefly  on  page  53.  The  fact  that  in  each  class  only  one  mono-sub- 
stitution product  of  ethane  is  known  has  been  given  as  proof  that  all 
of  the  hydrogen  atoms  in  ethane  are  alike,  i.e.,  ethane,  like  methane, 
is  a  symmetrical  compound.  When,  however,  two  substituting  elements 
or  groups  are  introduced  into  ethane,  two  isomeric  compounds  result 
each  having  the  composition  C2H4C12,  in  the  case  of  the  chlorine 
product, 

C2H6      +      2C12    -  >     C2H4C12      +      2HC1 

Ethane  Di-chlor  ethane 

Unsymmetrical  Di-chlor  Ethane.  —  These  two  compounds  may  also 
be  prepared  by  other  reactions  which  show  us  what  their  true  consti- 
tution is.  When  acet-aldehyde,  which  we  have  previously  proven  has 
the  constitution  represented  by  the  formula,  CH3  —  CHO,  is  treated 
with  phosphorus  penta-chloride  one  oxygen  atom  is  replaced  by  two 
chlorine  atoms  and  the  product  is  one  of  the  two  isomeric  di-chlor 
ethanes. 


CH3—  CHO  +  PC15    -  >    CH3—  CHClo  +  POC13 

Aldehyde  Di-chlor  ethane 

This  reaction  is  entirely  different  from  that  of  phosphorus  penta-chlo- 
ride on  alcohol,  in  which  the  hydroxyl  of  the  alcohol  is  replaced  by  one 
chlorine,  and  the  mono-halogen  substitution  product  of  the  hydrocarbon 
results  (p.  81).  If  our  ideas  in  regard  to  the  constitution  of  aldehyde 
are  correct,  this  reaction  must  mean,  that,  in  the  di-chlor  ethane  formed 
in  this  way,  the  two  chlorine  atoms  are  linked  to  the  same  carbon  atom. 
Such  a  structure  represents  a  compound  which  is  plainly  unsymmetrical. 

Symmetrical  Di-chlor  Ethane.  —  The  isomeric  di-chlor  ethane  is 
obtained  when  the  unsaturated  hydrocarbon  ethylene,  or  ethene  takes 
up  two  chlorine  atoms,  forming  an  addition  product. 

According  to  our  ideas  in  regard  to  the  constitution  of  the  hydro- 
carbon ethane  the  only  formula  for  an  isomeric  di-chlor  ethane,  differing 
from  the  one  derived  from  aldehyde,  is  one  in  which  the  two  chlorine 
atoms  instead  of  being  both  linked  to  the  same  carbon  atom  are  each 
linked  to  a  different  carbon  atom.  This  gives  us  a  symmetrical  com- 


POLY-HALIDES  189 

pound  corresponding  to  the  unsym metrical  one  just  given.  The  two 
formulas  are: 

H    H  H     H 

CH3— CHC12  or  H— C— C— Cl        CH2C1— CH2C1  or  Cl— C— C— Cl 
H    Cl  H     H 

Ethylidene  chloride  Ethylene  chloride 

Unsymmetrical  di-chlor  Symmetrical  di-chlor 

ethane  ethane 

(from  aldehyde)  (from  ethylene) 

Ethylene  and  Ethylidene  Compounds. — The  fact  that  the  sym- 
metrical di-chlor  ethane  is  readily  prepared  from  ethylene,  has  given 
to  it  the  name  of  ethylene  chloride.  To  distinguish  the  two  isomers 
by  name  the  other,  the  unsymmetrical  di-chlor  ethane,  has  been  called 
ethylidene  chloride.  In  connection  with  our  discussion  of  the  consti- 
tution of  the  ethene  series  of  unsaturated  hydrocarbons  (p.  154),  we 
have  used  the  constitution  of  ethylene  chloride  as  proving  the  consti- 
tution of  ethylene  or  ethene,  as  H2C  =  CH2.  Isomerism  of  the  charac- 
ter shown  in  these  two  di-chlor  ethanes,  as  above  explained,  is  found  in 
all  classes  of  di-substitution  products  of  ethane,  so  that  we  may  express 
the  compounds  by  general  formulas  as  follows : 

CH3— CHX2  CH2X— CH2X 

Ethylidene  Compounds  Ethylene  Compounds 

Unsymmetrical  Symmetrical 

Ethylidene  Halides    CH3— CHX2 

The  ethylidene,  or  unsymmetrical  di-halogen  substitution  products 
of  ethane,  are  not  of  much  importance,  because  they  do  not  easily 
undergo  reaction.  They  are  prepared  by  the  reactions  just  described, 
viz.,  from  aldehyde  by  the  action  of  phosphorus  penta-chloride,  -bro- 
mide, or  -iodide.  Also  by  the  action  of  phosphorus  chlor-bromide, 
PCl3Br2,  or  of  carbonyl  chloride  (phosgene),  COC12.  They  may  also 
be  made  by  the  further  halogenation  of  the  mono-halogen  ethanes: 

CH3— CH2C1  +  C12    >    CH3— CHC12  +  HC1 

Ethyl  chloride  Ethylidene 

chloride 

This  last  reaction  is  of  interest  in  showing  that  a  second  halogen  atom, 
introduced  into  a  compound  which  already  has  one  substituted  halo- 
gen, enters  the  same  carbon  group  in  which  the  first  halogen  is  sub- 
stituted. The  reaction  is  not,  however,  all  one  way,  as  the  symmetrical 


190  ORGANIC  CHEMISTRY 

compound  is  also  obtained.  The  proportions  of  the  two  compounds 
depend  on  the  conditions  of  the  reaction  and  upon  the  particular  re- 
agent used. 

Ethylidene  Chloride. — CH3 — CHC12  is  a  colorless  liquid  boiling  at 
57.7°.  It  does  not  mix  with  water  and  possesses  anesthetic  properties, 
though  it  has  no  general  use  as  such.  It  is  a  by-product  in  the  manu- 
facture of  chloral,  tri-chlor  aldehyde  (p.  226). 

Ethylidene  Bromide.   CH3— CHBr2,  Ethylidene  Iodide,  CH3— CHI2. 

The  former  is  a  liquid  boiling  at  110.5°,  and  the  latter  a  liquid  boiling 
at  177°. 

Ethylene  Halides    CH2X— CH2X 

The  ethylene  halides  may  be  prepared  by  direct  halogenation  of 
ethane,  but  this  is  not  a  practical  method  as  it  yields  a  mixture  of 
the  two  isomeric  compounds  as  in  the  further  halogenation  of  the 
monohalogen  ethanes.  The  best  method  of  preparation  is  from  the 
unsaturated  hydrocarbon,  ethylene.  This  reaction  has  been  fully 
considered  already  (p.  154)  and  need  not  be  discussed  again. 

Reactions. — The  ethylene  halides,  especially  ethylene  bromide,  are 
very  important  synthetic  reagents,  as  they  readily  undergo  reaction. 
The  halogen  is  easily  replaced  by  the  hydroxyl  group,  ammo  group, 
cyanogen  group,  etc.,  yielding  the  corresponding  symmetrical  or  ethylene 
di-substitution  products,  as  follows: 

CH2Br— CH2Br  +  2KOH >  CH2OH  — CH2OH    +  2KBr 

CH2Br— CH2Br  +  2KCN  -4  CH2CN  — CH2CN    +  2KBr 

CH2Br— CH2Br  +  2HNH2  -»  CH2NH2— CH2NH2  +  2KBr 

CH2Br— CH2Br  +  2KSH  — >  CH2SH  — CH2SH    +  2KBr 
etc.                                                     etc. 

Ethylene  bromide  Symmetrical  di- 

substituted  ethanes 

The  most  important  reactions  of  the  ethylene  halides  are  those  in  a 
series  that  takes  place  with  the  loss  of  hydrogen-halide.  The  hydrogen 
and  the  halogen  are  lost  from  different  carbon  groups,  with  the  conver- 
sion of  the  saturated  di-halide  into  an  unsaturated  mono-halide,  as 
follows : 

CH2— CHBr        _HBr       CH2  =  CHBr 

j  ¥         Mono-brom  ethylene 

(Br     H) 

Ethylene  bromide 


POLY-HALIDES  1  91 

The  unsaturated  compound  may  then  take  up  two  halogen  atoms, 
like  the  ethylene  hydrocarbons  themselves,  going  back  again  to  the 
saturated  class  of  compounds, 


=  CHBr  +  Br2    -  >     CH2Br—  CHBr2 

Mono-brom  ethylene  Tri-brom  ethane 

We  thus  obtain  a  tri-halogen  substitution  product  of  the  saturated 
hydrocarbon.  These  reactions  may  be  repeated,  yielding,  each  time, 
a  halogen  product  of  the  saturated  hydrocarbon  containing  one  more 
halogen  atom.  We  may  thus  pass  from  di-halogen  ethane  to  hexa- 
halogen  ethane.  The  entire  series  of  reactions  is  as  follows: 


CH2Br— CH2Br   _"    CH2=CHBr  +  Br2  >  CH2Br— CHBr2 

Ethylene  bromide 
Di-brom  ethane  (Sym) 

CH2Br— CHBr2  ZS*  CH2=CBr2    +  Br2  -  — >  CH2Br— CBr3 
or  CHBr  =  CHBr  or  CHBr2— CHBr2 

TJ"D- 

CH2Br— CBr3     _fl^      CHBr=CBr2  +  Br2  >  CHBr2— CBr3 

or     CHBr2— CHBr2 

CHBr2— CBr3    H5^r    CBr2  =  CBr2  +  Br2 »  CBr3— CBr3 

Hexa-brom  ethane 

One  more  reaction  of  the  ethylene  halides  must  be  mentioned,  as,  in 
it,  we  have  a  direct  proof  that  the  structure  of  ethane  is  as  represented, 
viz.,  the  symmetrical  structure.  Our  evidence  of  this  structure,  thus 
far  is  simply  indirect,  i.e.,  from  the  proof  that  the  other  isomeric 
di-halogen  ethane  has  the  unsymmetrical  structure. 

When  ethylene  bromide  is  oxidized brom-acetic  acid  is  obtained,  i.e., 
acetic  acid  in  which  bromine  is  substituted  in  the  methyl  radical,  CH2- 
Br — COOH.  Such  a  compound  can  result  only  from  a  di-brom  ethane 
in  which  the  two  bromine  atoms  were  originally  linked  to  different  car- 
bon atoms,  viz.,  CH2Br — CH2Br.  By  oxidation  one  of  the  carbon 
groups,  containing  one  bromine  atom  is  converted  into  carboxyl,  and 
the  other,  still  containing  one  tromine  atom  and  one  only,  remains. 
The  same  compound  is  also  obtained  with  intermediate  products,  when 
one  of  the  halogen  atoms  is  first  replaced  by  hydroxyl  and  then  subjected 
to  oxidation.  The  replacement  of  one  halogen  by  hydroxyl  would  yield  a 
compound  containing  primary  alcohol  group  ( — CH2OH)  which  on 
oxidation  would  be  converted  first  into  the  aldehyde  group  ( — CHO) 


1 92  ORGANIC  CHEMISTRY 

and  this  by  further  oxidation,  into  the  acid  group  ( — COOH)  as  follows, 
in  the  case  of  the  chlorine  compound : 

CH2C1— CH2C1    >     CH2C1— CH2OH    jt_° 

Ethylene  chloride 

CH2C1— CHO    lL£    CH2C1— COOH 

Chlor  aldehyde  Chlor  acetic  acid 

Higher  Halogen  Ethanes 

Of  the  higher  halogen  derivatives  of  ethane,  representatives  of  the 
tri-,  tetra-,  penta-  and  hexa-derivatives  are  known.  Of  the  tri-  and  penta- 
halogen  ethanes  only  one  class  is  known,  viz.,  the  unsymmetrical,  i.e., 
CH3— CX3  or  CH2X— CHX2,  and  CHX2— CX3.  Of  the  tetra-halogen 
ethanes  the  symmetrical  and  the  unsymmetrical  are  both  known, 
"exactly  analogous  to  ethylene  chloride  and  ethylidene  chloride: 

CHX2— CHX2  CH2X— CX3 

Symmetrical  Tetra-halogen  ethanes  Unsymmetrical 

The  hexa-halogen  ethanes,  CX3 — CX3,  or  per-halogen  ethanes,  are 
known  in  both  the  chlorine  and  the  bromine  compounds.  Per-chlor 
ethane,  CC13 — CC13,  hexa-chlor  ethane  is  a  colorless,  crystalline  sub- 
stance with  a  camphor-like  odor  and  which  melts  at  184°.  Per-brom 
ethane,  CBr3 — CBr3,  hexa-brom  ethane  is  also  a  colorless,  crystalline 
substance. 


B.  POLY-CYANIDES 

The  next  group  of  poly-substitution  products  are  those  containing 
two  or  more  cyanogen  radicals,  ( — CN).  These  correspond  exactly 
to  the  poly-halogen  compounds,  from  which  they  may  be  prepared  by 
the  action  of  potassium  cyanide. 

CH3— CHC12  +   2KCN    >     CH3— CH(CN)2    +    2KC1 

Ethylidene  chloride  Ethylidene  cyanide 

CH2C1— CH2C1  -f  2KCN      >    CH2(CN)— CH2(CN)  -f-  2KC1 

Ethylene  chloride  Ethylene  cyanide 

These  compounds  are  characterized  by  the  same  properties  as  the 
mono-cyanogen  compounds.  As  the  latter  are  known  as  acid  nitriles, 
because  on  hydrolysis  they  yield  mono-carboxy  acids,  so  also  the  di- 
cyanogen  compounds  are  nitriles  of  the  di-carboxy  acids.  The  symmetri- 


POLY-CYANIDES    AND    -AMINES  193 

cal  di-cyanogen  ethane  or  ethylene  cyanide  yields  a  di-carboxy  acid 
known  as  succinic  acid 

CH2— CN  CH2— COOH 

+  4H2O >  +  2NH3 

CH2— CN  CH2— COOH 

Succinic  acid  nitrile  Succinic  acid 

Ethyleae  cyanide 

These  di-cyanogen  and  other  poly-cyanogen  derivatives  are  of  impor- 
tance only  in  this  connection  as  nitriles  of  the  poly-carboxy  acids  and  those 
that  are  necessary  to  be  considered  will  be  referred  to  later  as  we  come 
to  them  in  the  study  of  these  acids.  The  simplest  di-cyanogen  com- 
pound is  the  gas  cyanogen  NC — CN,  which  has  been  referred  to  as  an 
example  of  a  radical  which  exists  as  such  in  the  free  state. 

C.  POLY-AMINES 

Putrescine  and  Cadaverine. — The  poly-amines  may  be  obtained  by 
the  reduction  of  poly-nitro  compounds  or  poly-cyanogen  compounds  (pp. 
70,  75).  In  the  former  case  the  amine  has  the  same  number  of  carbons 
as  the  nitro  compound  but  in  the  latter  case  the  amine  has  two 
more  carbons  than  the  radical  of  the  di-cyanogen  compound.  The 
usual  method  of  formation,  however,  is  the  one  already  used  in  pre- 
paring the  mono-amines,  viz.,  from  the  corresponding  halogen  com- 
pound by  action  of  ammonia. 

CH2— CH2Br  CH2— CH2— NH2 

|  +  2NH3       — *      |  +  2HBr 

CH2— CH2Br  CH2— CH2— NH2 

i-4-Di-brom  butane  Putrescine 

i-4-Di-amino  butane 

CH2— CN  CH2— CH2— NH2 

CH2  -|-  4H2         >         CH2 

I  I 

CH2— CN  CH2— CH2— NH2 

i-3-Di-cyano  propane  Cadaverine 

i-5-Di-amino  pentane 

The  di-amines  are  strong  di-acid  bases  with  ammoniacal  odor  and 
readily  form  salts  with  acids.  The  di-amines  of  the  higher  hydro- 
carbons, in  which  the  two  amine  groups  are  attached  to  the  end 
carbon  atoms,  are  known  as  poly-methylene  compounds  because  all  of 

13 


IQ4  ORGANIC  CHEMISTRY 

the  carbon  hydrogen  groups  are  ( — CH2 — ).  They  exhibit  an  inter- 
esting property  of  losing  ammonia  and  yielding  an  anhydride-like 
compound.  The  reaction  takes  place  with  the  hydrochloric  acid  salts. 

CH2— CH2— (NH2  -NH3  CH2— CH2v 

I  I  >H. 

CH2— CH2— NH(H  CH2— CH/ 

Putre  seine  Pyrrolidine 

Tetra-methylene  di-amine 

Imines. — The  compounds  so  formed  and  containing  the  group 
( — NH — ),  are  known  as  imines.  The  four  carbon  imine  given  above 
is  named  pyrrolidine,  and  the  di-amine  from  which  it  is  formed,  as 
tetra-methylene  di-amine,  also  as  putrescine.  It  is  found  as  a  putre- 
faction product  of  animal  flesh.  The  analogous  five  carbon  compounds 
are,  penta-methylene  di-amine,  or,  cadaverine,  and  the  imine  is  piperi- 
dine.  The  last  compound  is  found  in  pepper  in  combination  as  the 
alkaloid,  piperine. 

CH2— CH2— (NH2  CH2— CH2  . 

|  -NH3  | 

CH2  CH2  >NH 

I  I  / 

CH2— CH2— NH(H  CH2— CH2 

Cadaverine  Piperidine 

Penta-methylene  di-amine 

Hetero-cyclic  Compounds. — In  the  formation  of  these  imines  the 
open  chain  structure  of  the  di-amine  compound  is  converted  into  a 
closed  chain,  or  ring  structure  of  the  imine.  As  the  ring  thus  formed 
contains  not  only  carbon  groups  but  also  a  nitrogen  group  the  com- 
pounds are  termed  hetero-cyclic.  These  compounds  are  of  importance, 
and  will  be  used  later,  in  showing  the  connection  between  the  two  great 
classes  of  organic  compounds,  viz.,  the  open  chain,  or  acyclic  compounds, 
such  as  the  saturated  and  unsaturated  compounds  which  we  have  been 
studying,  and  the  closed  chcin,  or  cyclic  compounds,  which  we  shall 
study  later,  in  connecton  with  benzene  and  its  derivatives. 


VII.  POLY-HYDROXY  COMPOUNDS— POLY-APCOHOLS 

A.  DI-HYDROXY  ALCOHOLS— GLYCOLS 
Glycol    HO— H2C— CH2— OH    Ethylene  Glycol 

When  alkyl  monohalides  are  treated  with  silver  hydroxide,  AgOH, 
or  with  potassium  hydroxide,  KOH,  the  halogen  is  replaced  by  the 
hydroxyl  group  and  mono-hydroxy  alcohols  result. 

R— CH2Cl  +  AgOH    >    R—  CHoOH  +  AgCl 

Alkyl  halide  Alcohol 

In  a  similar  way,  when  ethylene  bromide  is  treated  with  silver 
acetate,  CH3 — COOAg,  an  acyl-ester  of  the  corresponding  di-hydroxy 
alcohol  is  obtained,  which,  on  hydrolysis,  yields  the  di-hydroxy  alcohol 
itself,  as  follows: 

CH2— (Br  +  Ag)— OOC— CH3        CH2— (OOC— CH3  +  H)— OH 

I  -2AgBr     I  +2NaOH 

CH2— (Br  +  Ag)— OOC— CH3        CH2—  (OOC— CH3  +  H)— OH 

Ethylene  Silver  acetate  Ester 

bromide 

CH2— OH 

|  +  2CH3— COONa  +  2H20 

CH2— OH 

Glycol 
Di-hydroxy  ethane 

Glycol. — This  synthesis  of  di-hydroxy  ethane  was  discovered  by 
Wurtz,  in  1854.  The  compound  was  named  by  him,  glycol,  because 
of  its  sweet  taste.  It  is  known  also  as  ethylene  glycol.  The  synthesis 
may  be  modified  by  substituting  potassium  acetate  for  the  silver  salt. 
Also,  ethylene  bromide  is  converted  directly  into  the  di-hydroxy 
compound,  by  boiling  with  dilute  potassium  carbonate. 

CH2— Br  CH2— OH 

|  +  K2CO3  -f  H20     — >     |  +  2KBr  +'  CO2 

CH2— Br  CH2— OH 

Ethylene  .  Ethylene  glycol 

Lbromide 

195 


196  ORGANIC  CHEMISTRY 

Glycol,  is  a  sweet,  colorless,  heavy  liquid,  boiling  at  195°,  and  with 
specific  gravity  of  1.128  at  o°.  It  is  miscible  with  water  or  alcohol  and 
is  slightly  soluble  in  ether. 

The  di-hydroxy  ethane  corresponding  to  ethylidene  chloride,  i.e., 
the  unsymmetrical  compound,  is  not  known.  It  will  be  recalled  that 
the  method  of  preparing  the  ethylidene  chloride  is  from  acet-aldehyde 
by  treatment  with  phosphorus  penta-chloride: 


CH3—  CHO  +  PCls    --  >    CH3—  CHC12  +  POC13 

Acet-aldehyde  Ethylidene  chloride 

If,  on  treatment  of  this  ethylidene  chloride  with  silver  hydroxide, 
a  corresponding  unsymmetrical  di-hydroxy  compound  was  obtained, 
it  would  correspond  to  the  formula,  CH3  —  CH(OH)2.  That  is,  two 
hydroxyl  groups  would  be  linked  to  the  same  carbon  atom.  In  the 
discussion  of  the  oxidation  products  of  alcohols  (p.  115)  the  reactions 
are  represented  as  taking  place  in  steps,  by  the  conversion  of  each 
hydrogen  of  an  original  methyl  group  into  hydroxyl.  As  soon,  however, 
as  two  hydroxyl  groups  are  produced  united  to  one  carbon  atom,  water 
is  lost  and  an  aldehyde  results.  Therefore,  if  such  a  product  was 
obtained  from  the  ethylidene  chloride,  as  indicated  above,  it  would 
immediately  lose  water  and  aldehyde  would  be  the  product.  This  is, 
in  fact,  the  case.  The  non-existence  of  an  ethylidene  glycol,  or  unsym- 
metrical di-hydroxy  ethane,  is  in  accordance  with  this  view,  that  more 
than  one  hydroxyl  group  linked  to  one  carbon  does  not  form  a  stable  compound. 

The  glycols  form  well  characterized  esters  and  ethers  in  which  one, 
or  both,  hydroxyl  groups  may  be  affected,  thus  yielding  mixed  com- 
pounds, i.e.,  alcohols  and  esters  or  ethers  combined,  also  di-esters  and 
di-ethers. 

Higher  Glycols 

With  the  higher  members  of  the  paraffin  hydrocarbons  we  have 
isomerism,  due  to  the  different  positions  in  which  the  two  hydroxyl 
groups  are  found.  Propane,  for  example,  yields  two  di-hydroxy 
derivatives,  viz., 

CH3—  CH(OH)—  CH2(OH)          CH2(OH)—  CH2—  CH2(OH) 

Propylene  glycol  Tri-methylene  glycol 

i-2-Di-hydroxy  propane  i-3-Di-hydroxy  propane 

(a-/3-Glycol)  (a-7-Glycol) 


DI-   AND    TRI-HYDROXY   ALCOHOLS  197 

DI-VALENT  MERCAPTANS,  THIO-GLYCOLS 

The  sulphur  analogues  of  the  glycols,  i.e.,  thio-glycols,  or  di-valent 
mercaptans  are  definitely  known  compounds.  Furthermore,  it  is 
found,  that  when  sulphur  replaces  oxygen,  in  compounds  of  this  class, 
two  sulph-hydrogen  groups  (  —  SH),  may  be  linked  to  one  carbon  atom 
and  a  stable  compound  result. 

Methylene  mercaptan,  CH2  =  (SH)2,  is  a  well  known  compound 
and  may  be  made  from  formaldehyde  by  treatment  with  hydrogen 
sulphide: 

H—  CH(O  +  2H)—  SH   -  >     H-CH(SH)2,  or,  CH2  =  (SH)2+H2O 

Formaldehyde  Methylene  mercaptan 

Similarly  ethylidene  mercaptan  may  be  obtained  from  acetaldehyde  ' 
CH3—  CH(O  +  2H)-  SH    -  >     CH3—  CH(SH)2  +  H20 

Acetaldehyde  Ethylidene 

mercaptan 

Mercaptals  and  Mercaptols.  —  Ethylidene  mercaptan  is  ordinarily 
obtained  as  the  thio-ether  by  the  action  of  ethyl  mercaptan  on  acet- 
aldehyde: 

,SC2H5 
CH3—  CH(O  +  2H)S—  C2H5       -4     CH3—  CH/ 

Acetaldehyde  Ethyl  mercaptan  XSO  H 

Acetaldehyde  ethyl  mercaptal 

Such  a  di-thio-ether  is  known  as  a  mercaptal  and  this  particular  one  is 
known  as  di-thio  acetal  (p.  117).  Analogous  compounds  obtained 
from  ketones,  e.g.,  from  acetone,  are  called  mercaptols. 


3. 

)C(0  +  2H)S—C2H5  —  >               C               +  H20 

CH/  CH/     XSC2H5 

Acetone  Acetone  ethyl  mercaptol 

Like  the  mono-thio-ethers,   these  di-thio-ethers  yield  sulphones, 
i.e.,  di-sulphones,  on  oxidation. 

C2H5—  S—  C2H5  +  O2  -  >.    C2H5—  SO2—  C2H5 

Di-ethyl  thio-ether  Di-ethyl  sulphone 

,S  —  C2Hs  ySO2  —  C2Hs 

CH3—  CH/                +  202  -  >      CH3—  CH/ 

XS—  C2H5  XSO2—  C2H5 

Acetaldehyde  ethyl  mercaptal  Di-ethyl  di-sulphone  methyl  methane 


198  ORGANIC  CHEMISTRY 

S—  C2H5  CH3  S02—  C2H5 


S—  C2H5  CH3  S02—  C2H5 

Acetone  ethyl  mercaptol  Di-ethyl  di-sulphone  di-methyl  methane 

Sulphonal 

Sulphonal.  —  This  last  compound  is  known  as  sulphonal,  and  is  an 
important  medicinal  substance  possessing  soporific  properties.  It  is  a 
solid  forming  colorless  crystals  which  melt  at  125°-!  26°.  It  is  soluble 
in  alcohol  and  in  hot  water,  slightly  in  cold. 


B.  TRI-HYDROXY  ALCOHOLS 
Glycerol    HOCH2— CH(OH)— CH2OH 

As  more  than  one  hydroxyl  group  linked  to  a  single  carbon  atom 
results  in  an  unstable  compound,  the  simplest  di-hydroxy  alcohol  is 
the  one  derived  from  the  two  carbon  hydrocarbon  ethane  (i.e.)  di- 
hydroxy  ethane,  or  glycol,  CH2-(OH)-CH2(OH).  Similarly  the 
simplest  tri-hydroxy  alcohol  is  derived  from  the  three  carbon  hydro- 
carbon propane.  It  is  known  commonly  as  glycerin,  but  is  better 
termed  glycerol,  as  the  termination,  ol,  signifies  an  alcohol. 

^,  CH2-OH 

Glycerol 
CH2(OH)-CH(OH)-CH2(OH)   or    CH -OH  Tri-hydroxy  propane 

Propan-tri-ol 
CH2-OH 

Synthesis  from  Propane. — The  constitution  of  glycerol  has  been 
established  by  a  series  of  reactions,  as  follows:  When  secondary,  or 
iso-propyl  alcohol,  propan-ol-2,  is  dehydrated  an  unsaturated  com- 
pound is  formed,  viz.,  propene,  the  three  carbon  member  of  theethylene 
series  of  hydrocarbons.  When  propene  is  treated  with  halogens,  e.g., 
chlorine,  two  atoms  of  the  halogen  add  on  directly  and  a  saturated 
di-chlor  compound  results  (see  p.  158). 

This  compound,  on  further  chlorination  by  means  of  iodine  mono- 
chloride,  IC1,  yields  tri-chlor  propane.  On  heating  with  water  this 
hydrolyzes  and  three  hydroxyl  groups  take  the  place  of  the  three 
chlorine  atoms. 


DI-   AND    TRI-HYDROXY   ALCOHOLS 


199 


Writing  the  reactions  in  one  scheme  we  can  follow  the  relationship 
very  readily. 


CH3 

I 
CH2 

CH3    • 

Propane 


CH3  CH2(H)  CH2 

+AgOH    !  -H2O   || 

CHC1         ~~"      CH(OH)         —*     CH 


CH8 

2-Chlor 
propane 


CH3 

Propan-ol-2 


CH8 

Propene 


CH2C1 

! 

CHC1 


CH3 

i-2-Di-chlor 
propane 


CH2(C1  CH2-OH 

|  +3H)OH      | 

CH(C1  7T'        CH  -OH 


CH2(C1 

i-2-3-Tri-chlor 
propane 


CH2-OH 

i-2-3-Tri-hydroxy 
propane 


Glycerol  must  be,  therefore,  i-2-3-tri-hydroxy  propane,  as  repre- 
sented bp  the  above  formula. 

Properties. — It  is  a  thick  syrup-like  liquid  more  or  less  oily  in  its 
feeling  and,  on  this  account,  was  at  one  time  called  an  oil.  It  is  not, 
however,  an  oil  but  a  true  alcohol  though  as  we  shall  see,  it  is  directly 
and  intimately  related  to  the  vegetable  and  animal  fats  and  oils.  It  is 
colorless,  odorless  and  very  hygroscopic.  It  has  a  sweet  taste  similar 
to  that  of  the  di-hydroxy  compound,  glycol,  and  mixes  in  all  propor- 
tions with  water  and  with  alcohol,  indicating,  thus,  its  alcohol  character. 
It  is  a  stable  compound  and  dissolves  many  organic,  and  some  inorganic 
substances.  It  is  non-irritating,  softens  the  skin,  when  applied  to  it, 
and  is  used  as  a  solvent,  or  medium,  in  which  many  medicinal  sub- 
stances are  taken  internally.  All  of  these  properties  give  it  many 
important  uses  both  in  the  industries  and  in  medicine.  When  cooled 
for  a  long  time  to  o°,  it  crystallizes,  the  crystals  melting  again  at  17°. 
It  boils,  undecomposed,  at  290°,  and  has  a  specific  gravity  of  1.2.  In 
its  chemical  properties,  glycerol  acts  as  an  alcohol,  forming  derivatives 
characteristic  of  alcohols.  As  may  be  seen,  from  its  constitution,  it 
contains  both  primary  and  secondary  alcohol  groups.  Its  derivatives, 
therefore,  are  characteristic  of  both  of  these  classes  of  alcohols. 


200  ORGANIC  CHEMISTRY 

DERIVATIVES  OF  GLYCEROL 
i.  SALTS 

Analogous  to  the  alkali  salts  of  the  alcohols,  e.g.,  C2H5  — ONa, 
sodium  ethylate,  glycerol  forms  salts  with  several  of  the  metals,  in 
which,  one,  two  or  three  of  the  hydroxyl  hydrogen  atoms  are  replaced 
by  metals.  Both  a  mono-sodium  and  a  di-sodium  glycerate  are  known. 
The  most  important  salt  of  glycerol  is,  perhaps,  the  lead  salt.  -  Lead 
being  bi-valent,  replaces  two  hydrogens  and  may  form  compounds 
represented  by  the  two  following  formulas: 

CH2-OX  CH2-0X 

|  \         Lead  glycerate      |  )Pb 

CH   -  OH  X,Pb  CH   -  OX 


CH2  -  O7  CH2  -  OH 

2.  ETHERS 

Glycerol  also  forms  ethers  with  ethyl  alcohol  and  all  three  of  the 
possible  ones  are  known. 

CH2O  -  C2H5  CH2O  -  C2H5  CH2O  -  C2H5 

I  I  ! 

CHOH  CHO  -  C2H5  CHO  -  C2H5 

I  I  ! 

CH2OH  CH2OH  CH20  -  C2H5 

Glyceryl  mono-  Glyceryl  di-ethyl  Glyceryl  tri-ethyl 

ethyl  ether  ether  ether 

3.  OXIDATION  PRODUCTS 

As  glycerol  contains  both  primary  and  secondary  alcohol  groups,  the 
oxidation  products  will  include  aldehydes,  ketones  and  acids,  and  the 
latter  may  be  either  mono-  or  di-basic.  On  complete  oxidation  the  prod- 
ucts are  formic  acid  and  carbon  dioxide.  The  most  important  of  the 
oxidation  products  are  the  two  obtained  when  the  lead  salt  of  glycerol 
is  oxidized  by  means  of  bromine  and  the  lead  then  replaced  by 
hydrogen.  As  the  lead,  in  the  lead  salt,  protects  two  of  the  carbon 
groups  and  prevents  their  being  oxidized,  only  one  of  the  original  alcoholic 
groups  will  be  oxidized.  As  this  may  be  in  one  case  a  primary  alcohol 
group  and  in  the  other  a  secondary  alcohol  group,  we  may  obtain, 


ESTERS    OF   GLYCEROL  2OI 

from  such  oxidation  either  an  aldehyde  or  a  ketone  compound.     This 
will  be  clear  from  the  following  reactions: 

O  CH2— OH 


CH  —OH  )Pb      Lead  glycerate       CH  —  O 

I  I 

CH2— O7  CH 

oxidation  and  then  re- 
placement of  Pb  by  H 

CH2— OH  CHO 

C  =  O  CH— OH 

I 
CH2— OH  CH2— OH 

Di-hydroxy  acetone  Glyceric  aldehyde 

Glycerose. — These  two  products,  the  aldehyde  and  the  ketone  of 
glycerol,  are  of  especial  importance,  as  we  shall  see  later,  because  a 
mixture  of  the  two  known  as  glycerose  is  the  simplest  of  the  large  and 
very  important  class  of  compounds  known  as  the  carbohydrates,  of 
which  the  sugars  form  a  subdivision.  On  further  oxidation  of  glyceric 
aldehyde  the  aldehyde  group  becomes  converted  into  the  carboxyl  group 
and  an  acid  results,  known  as  glyceric  acid.  CH2(OH) — CH(OH)— 
COOH.  In  a  similar  way  the  other  primary  alcohol  group  may  be 
oxidized  to  carboxyl  and  a  di-basic  acid  obtained,  HOOC — CH(OH) — 
COOH,  hydroxy  malonic  acid.  These  will  all  be  considered  again  later 
when  we  discuss  the  hydroxy  acids. 

4.  INORGANIC  ACID  ESTERS 

By  far  the  most  important  group  of  derivatives  of  glycerol  is  that  of 
the  esters  or  ethereal  salts.  Just  as  ethyl  alcohol  and  hydrochloric  acid 
yield  an  ester,  C2H5 — Cl,  ethyl  chloride,  so  glycerol  yields  derivatives 
in  which  the  hydroxy  1  groups  are  replaced  by  halogens.  These  com- 
pounds are  formed,  both  by  the  action  of  the  hydro-halogen  acid,  and 
also,  by  the  action  of  the  phosphorus  tri-halogen  compounds,  e.g., 
phosphorus  tri-chloride,  PCls 

CH2(OH)— CH(OH)— CH2(OH)  +  H— Cl    > 

Glycerol 

CH2(OH)— CH(OH)— CH2— Cl  +  H2O 

Glyceryl  mono-chloride 
Mono-chlor  hydrine 


202  ORGANIC  CHEMISTRY 

Hydrines. — Such  a  compound  is  known  as  a  halogen  hydrine,  or 
more  specifically  as  a  chlor  hydrine.  All  three  of  the  chlor  hydrines, 
viz.,  the  mono-,  di-  and  tri-chlor  hydrines  are  known,  as  follows: 

CH2— Cl  CH2— Cl  CH2— Cl 

!  I  I 

CH— OH  CH— Cl  CH— Cl 

I 
CH2— OH  CH2— OH  CH2— Cl 

Mono-chlor  hydrine  Di-chlor  hydrine  Tri-chlor  hydrine 

i-2-3-Tri-chlor  propane 

The  tri-chlor  hydrine  is  plainly  tri-chlor  propane,  a  simple  tri-halogen 
substitution  product  of  propane.  It  has  already  been  mentioned  in 
connection  with  the  synthesis  of  glycerol  from  propane.  Of  the  esters 
which  glycerol  yields  with  the  inorganic  acids  those  formed  with  nitric 
acid  are  the  most  important. 

CH2OH— CHOH— CH2(OH  +  H)— ONO2    — * 

Glycerol 

CH2OH— CHOH  -CH2— ON02 

Glyceryl  mono-nitrate 

Nitric  Acid  Esters. — All  three  of  the  nitrates  are  known  and  when 
glycerol  is  completely  nitrated  it  is  the  tri-nitrate  which  is  formed. 

CH2— (OH  CH2— ONO2 

+  3H)— ON02         | 
CH— (OH  ~~*  CH— ONO2 

i  I 

CH2— (OH  CH2— ONO2 

Glycerol  Glyceryl  tri-nitrate 

Nitro-glycerin 

Nitro  Glycerin. — Glyceryl  tri-nitrate  is  the  common  and  valuable 
explosive  commonly  known  as  nitre-glycerin.  It  is  prepared  by  treat- 
ing glycerol  with  a  mixture  of  nitric  and  sulphuric  acids.  The  nitro- 
glycerine separates  as  an  oily  liquid  which  is  colorless  and  odorless  but 
has  a  burning  sweet  taste.  It  is  insoluble  in  water  but  soluble  in 
alcohol  and  in  benzene.  It  solidifies  at  8°.  It  is  poisonous  but  in 
small  doses  is  an  important. medicine,  acting  as  a  heart  stimulant. 

Dynamite. — The  most  important  property  of  the  substance  is  its 
great  explosive  power  when  detonated.  It  can,  however,  be  burned 
glowly  without  exploding.  As  an  explosive  it  is  not  generally  used  in 
its  pure  liquid  form  but  is  mixed  with  an  inactive  powder  material,  such 


FATS   AND   OILS  203 

as  infusorial  earth.  In  this  form,  known  as  dynamite,  it  retains  all 
of  its  explosive  properties  and  can  be  handled  more  easily  and  safely. 
If,  instead  of  mixing  nitro-glycerine  with  infusorial  earth  it  is  dissolved 
in  collodion,  which  is  a  nitrated  cellulose,  to  be  studied  later,  a  product 
is  obtained  known  as  gelatin  powder,  which  possesses  like  explosive 
properties  and  has  certain  practical  advantages. 

Nobel. — It  is  interesting  to  know,  that  both  of  these  practical  ap- 
plications of  nitro-glycerine,  viz.,  dynamite  and  gelatin  powder  were 
invented  by  a  Swede  by  the  name  of  Nobel  who  left  his  money  made 
from  the  invention  of  these  powerful  explosives,  for  the  establishment 
of  prizes  in  connection  with  the  promotion  of  peace  and  known  as  the 
Nobel  Peace  Prizes. 


5.  ORGANIC  ACID  ESTERS 
FATS  AND  OILS 

The  esters  which  glycerol  forms  with  the  organic  acids  of  the  open 
chain  series  or  fatty  acids  as  they  are  known,  are  of  especial  importance. 
They  are  the  chief  constituents  of  the  widely  distributed  natural  fats 
and  oils  of  the  animal  and  vegetable 'kingdoms.  The  oils  termed  min- 
eral oils,  do  not  belong  to  this  group,  but  are  hydrocarbons,  as  has  al- 
ready been  discussed,  (p.  40).  Just  as  glycerol  forms  mono-,  di- 
and  tri-acid  esters  with  the  inorganic  acids,  so  with  organic  acids,  it 
forms  esters  of  the  same  character.  With  acetic  acid,  e.g.,  we  have  the 
three  following  compounds,  which  illustrate  the  esters  of  glycerol  with 
organic  acids. 

CH2— OH  CH2— OOC— CH3  CH2— OOC— CH3  CH2— OOC— CH3 

I  ! 

CH— OH  CH— OH       CH— OH       CH— OOC— CH3 

I  I  I 

CH2— OH  CH2— OH       CH2— OOC— CH3  CH2— OOC— CH3 

Glycerol  Glyceryl  Glyceryl  Glyceryl 

mono-acetate  di-acetate  tri-acetate 

The  most  important  esters  of  this  class  are,  the  neutral  or  tri-acid 
esters  of  glycerol  with  the  higher  acids  of  the  saturated  and  the  unsatu- 
rated  series.  The  most  important  acids,  in  this  connection,  are  given 
in  the  following  list: 


2O4 


ORGANIC  CHEMISTRY 
ACIDS  OCCURRING  AS  ESTERS  IN  FATS  AND  OILS 


Saturated  acids 

Unsaturated  acids 

Hydrocarbon,  CnH2n  +  2 

Acid,  CnH2nO2 

Hydrocarbon,  CnHzn 

Acid(CnH2»_2)02 

Butyric  acid  

C3H7—  COOH 
C5HU—  COOH 
C7H15—  COOH 
C9H19—  COOH 
CnH23—  COOH 
C13H2r—  COOH 
C16H3i—  COOH 
Ci7H35—  COOH 
Ci9H39—  COOH 

Crotonic    and    iso-cro- 
tonic  acids  
Hypogaeic  acid  
Oleic  and  elaidic  acids  .  . 
Hydrocarbon,  C»H2n-2  
Linoleic  acid  
Hydrocarbon,  CnH2n-4  
Linolenic    and    iso-lin- 
olenic  acids     

C3H5—  COOH 
C15H29—  COOH 
C17H33—  COOH 

Add  (CnH2n-4)02 

C17H31—  COOH 

Acid  (CnH2n-6)02 

C17H29—  COOH 

Caproic  acid  
Caprylic  acid  
Capric  acid 

Laurie  acid  
Myristic  acid  
Palmitic  acid 

Stearic  acid  

Arachidic  acid  

Constitution  of  Fats  and  Oils. — These  acids  which  have  all  been  pre- 
viously discussed  (pp.  136  and  170)  embrace  the  more  common  ones  that 
are  found  as  esters  in  most  oils  and  fats.  The  tri-acid  ester  of  glycerol 
and  palmitic  acid  may  be  taken  as  an  example  of  a  typical  fat.  It  is 
exactly  analogous  to  the  ester  of  glycerol  and  acetic  acid  which  we  have 
just  considered,  and  its  formula  is: 


CH2— OOC— Ci5H8i 

! 

CH  — OOC— Ci5H3i 


CH2 — OOC — 


Glyceryl  tri-palmitate 
A  typical  fat 


These  esters  may  be  prepared  synthetically  by  reactions  already 
referred  to  in  connection  with  the  general  methods  for  the  preparation 
of  esters  (p.  143).  In  the  case  of  the  palmitic  acid  esters,  the  mono-,  di- 
and  tri-palmitates  have  all  been  prepared  by  these  synthetic  methods. 

Chevreul.  Berthelot. — The  most  important  fact,  however,  in 
connection  with  these  esters  of  glycerol  and  the  higher  fatty  acids,  is, 
that  they  are  found  in  such  wide  and  general  distribution  in  nature,  in 
the  form  of  fats  and  oils.  The  true  chemical  nature  of  animal  and 
vegetable  fats  and  oils  was  first  shown  by  the  French  chemist  Chevreul, 
in  1815  and  later  established  by  Berthelot  in  1860.  They  have  the 
constitution  of  glycerol  esters  of  the  higher  saturated  and  unsaturated 
acids.  The  different  fats  and  oils  are  distinguished  from  each  other 
by  the  different  acid  radicals,  and  the  different  proportions  of  them, 


FATS    AND    OILS 


205 


which  are  contained  as  component  parts  of  the  glycerol  esters.  Fats 
are  not  pure  chemical  individuals  but  are  mixtures  of  several  in  some 
cases  eight  or  ten,  different  esters.  While  the  acid  radical  components 
differ  the  alcohol  radical  component  is  always  the  same,  viz.,  that  of 
glycerol.  A  single  fat  may  contain  several  esters  but,  in  a  particular 
fat,  both  the  acid  radicals  present  and  the  proportions  of  them,  are 
definite  and  constant. 

Reactions  of  Fats  and  Oils.  —  The  most  important  reaction  of  fats 
and  oils  is  the  one  by  which  they  are  decomposed  into  their  constituent 
acids  and  glycerol.  By  this  reaction  the  particular  acid  or  acids  may 
be  determined  either  qualitatively  or  quantitatively. 

Hydrolysis.  —  When  an  ester  is  boiled  with  water,  or  with  water  and 
an  alkali  (p.  141)  it  is  decomposed  into  the  alcohol  and  acid  from  which 
it  is  derived.  The  alkali  present  converts  the  acid  into  the  corresponding 
salt  so  that  the  final  products  of  the  reaction  are  the  alcohol  and  the 
salt  of  the  acid. 


+  NaOH 
C2H5—  (OOC—  CH3  +  H)—  OH 

Ethyl  acetate 

C2H5—  OH    + 

Ethyl  alcohol 


CH3—  COONa 

Sodium  acetate 


H2O 


This  reaction,  it  will  be  recalled,  is  typical  of  all  esters,  or  ethereal 
salts.  Because  it  is,  in  fact,  a  reaction  due  to  the  action  of  water,  it 
is  known  as  hydrolysis.  It  is  the  reverse  of  the  reaction  of  esterification. 

Saponification. — With  a  fat,  which  is  a  glycerol  ester  of  a  higher  fatty 
acid,  typified  by  glyceryl  tri-palmitate,  the  reaction  yields  glycerol 
and  the  salt  of  the  acid,  or  acids,  present,  as  follews: 


CH2— (OOC— C15H3i 


H)— OH 


CH  —(OOC—  C 1 5H3i     +     H)-  OH 


CH2— (OOC— Ci5H 

Glyceryl  tri-palmitate 


H)— OH 
CH2— OH 


3NaOH 


Ci5H31— COONa 


CH— OH    +     Ci5H31— COONa     +  3H20 


CH2— OH 

Glycerol 


Ci5H3i— COONa 

Sodium  palmitate,  Soap 


206  ORGANIC  CHEMISTRY 

The  sodium  or  potassium  salt  of  palmitic  acid,  or  of  stearic  acid  or  the 
mixed  salts  of  several  acids  obtained  from  ordinary  fats,  is  the  common 
substance  known  as  soap.  This  particular  reaction  of  hydrolysis,  is, 
therefore,  known,  also,  as  a  reaction  of  saponification  (soap  formation)  . 
Strictly  speaking  the  reaction  of  saponification  applies  only  to  the 
alkaline  hydrolysis  of  fats,  i.e.,  of  glycerol  esters,  but,  as  the  hydrolysis 
of  other  esters  is  a  reaction  of  exactly  the  same  character,  the  term  is 
used  to  apply  equally  to  the  hydrolysis  of  any  ester  in  presence  of  an 
alkali.  In  the  case  of  the  lower  alcohol  and  lower  acid  esters,  e.g., 
ethyl  acetate,  the  salt  formed  is  not  a  soap  but  is  a  crystalline  salt, 
sodium  acetate. 

As  has  been  previously  discussed,  the  reactions  of  hydrolysis  and 
esterification  constitute  a  typical  reversible  reaction.  We  have,  then, 
the  two  following  examples  of  this  general  reversible  reaction: 

—  H—  OH 
C2H5—  OH    +     HOOC—  CH3  ^Z!  C2H5—  OOC—  CH3 

Ethyl  alcohol  Acetic  acid  _i_  TT  _  /-\TT  Ethyl  acetate 


CH2—  OH      HOOC—  Ci5H3i  CH2—  OOC— 

I  -3H-OH  | 
CH  —OH  +  HOOC—  Ci5H3i  ZIZL  CH  —  OOC—  Ci5H3i 

|  +3H-OH  | 
CH2—  OH  HOOC—  Ci5H31  CH2—  OOC—  Ci5H31 

Glycerol  Palmitic  acid  Glyceryl  tri-palmitate 

Typical  fat 

As  we  shall  see,  hydrolysis  takes  place  with  other  compounds  than 
esters  usually  in  the  presence  of  some  catalytic  agent,  such  as  enzymes, 
so  that  the  term  hydrolysis  refers  generally  to  the  decomposition  of  a 
compound  by  means  of  water,  while  saponification  refers  to  the  par- 
ticular hydrolysis  of  an  ester  by  means  of  water  in  the  presence  of  an 
alkali,  the  product  being  a  soap  or  a  crystalline  salt. 

As  commercially  made  by  the  saponification  of  fats,  soaps  are  not 
pure  chemical  individuals  but  consist  of  a  mixture  of  the  alkali-metal 
salts  of  the  several  fatty  acids  contained  as  esters  in  the  original  fat  or 
oil.  The  composition  of  soap,  therefore,  depends  upon  the  composition 
of  the  fat  from  which  it  is  made.  As  the  common  fats  and  oils  which 
are  used  for  this  purpose  contain,  mostly  the  glycerol  esters  of  palmitic, 
stearic  and  oleic  acids,  the  common  soaps  are  mixtures  of  sodium,  or 
potassium,  palmitate,  stearate  and  oleate.  We  shall  consider  now, 


FATS   AND    OILS  207 

the  composition  and  properties  of  some  of  the  more  common  and  im- 
portant fats  and  oils  of  animal  or  vegetable  origin. 

General  Properties  of  Fats  and  Oils. — Fats  differ  from  oils  simply 
in  their  physical  properties,  the  fats  being  solid  at  ordinary  tempera- 
tures while  the  oils  are  liquid.  They  both  have  exactly  the  same  gen- 
eral character  as  regards  their  chemical  composition  and  constitution, 
as  we  have  above  discussed.  The  acids  which  are  present  as  glycerol 
esters  are  the  mono-basic  acids  of  the  saturated  and  the  unsaturated 
series.  As  we  have  stated,  the  fats  and  oils  are  complex  mixtures  of 
several  esters,  in  some  cases  as  many  as  eight  or  ten  and  their  physical 
and  chemical  characters  will  depend,  therefore,  upon  the  characters 
of  the  different  esters  present  and  the  proportions  in  which  these  occur. 

Glycerol  Esters. — All  of  the  esters  present  in  fats  are  glycerol 
esters,  and,  in  most  cases,  the  neutral  or  tri-acid  ester.  The  character- 
istic thing  in  each  ester  is  therefore  the  particular  acid  radical  present. 
The  esters  of  fats  have  been  given  names  derived  from  those  of  the 
various  acids.  In  place  of  the  termination  ic  of  the  acid  we  use  the 
termination  in.  For  example,  the  tri-palmitic  acid  ester  of  glycerol, 
or,  glyceryl  tri-palmitate,  is  called,  tri-palmitin,  or,  simply  palmitin. 
Similarly  the  esters  of  stearic,  oleic  and  butyric  acids  are  called,  stearin, 
olein,  and  butyrin.  The  prefixes,  mono,  di,  and  tri  are  also  used  to  in- 
dicate whether  the  ester  has  one,  two  or  three  acid  groups  present. 
The  properties  of  a  fat,  therefore,  which  contains  a  mixture  of  palmitin, 
olein,  and  stearin  will  correspond  to  the  properties  of  these  individual 
esters  according  to  the  proportions  in  which  they  are  present.  Some  of 
these  esters  have  never  been  prepared  in  a  pure  state,  so  that  we  know 
of  their  properties  only  in  a  general  way,  as  deduced  from  those  of  the 
fats  in  which  they  are  present. 

Table  XV  gives  the  more  common  esters,  the  fats  in  which  they  are 
most  abundant,  and  the  corresponding  acids,  with  the  properties  of 
each  so  far  as  determined. 

Analytical  Methods. — For  purposes  of  identification  and  analysis 
the  distinguishing  properties  and  reactions  of  fats  depend  upon  the 
properties  of  the  esters  of  which  they  are  composed  and  also  upon  those 
of  the  acids  which  result  on  saponification.  While  it  is  not  the  purpose 
of  this  study  to  discuss  methods  of  analysis  we  shall  mention,  briefly,  the 
most  important  properties  and  reactions  of  the  fats  by  means  of  which 
they  may  be  identified  or  analyzed.  For  more  detailed  information  in 


208 


ORGANIC  CHEMISTRY 


TABLE  XV. — GLYCEROL  ESTERS,  FATS 


Ester 

M.P. 

B.P. 

Fat  or  Oil 

M.P.  or  S.P. 

Properties 

Saturated  Series 
Butyrin 

285° 

Butter  fat 

29°,      35° 

Non-drying 

Cocoanut  oil 

20°,         28° 

Non-drving 

Caprylin 

Butter  fat 
Cocoanut  oil 

29°,      35° 

20°,         28° 

Non-drying 
Non-drying 

Human  fat 

Non-drying 

Caprin                     

Butter  fat 
Goats-milk  fat 

29°,      35° 

Non-drying 
Non-drying 

Liiurin 

Cocoanut  oil 
Cod-liver  oil 
Butter  fat 
laurel  oil 

20°,         28° 

liquid 
29°,      35° 
32°,      36° 

Non-drying 
Non-drying 
Non-drying 
^on-drying 

JVEyristin              

53° 

Cocoanut  oil 
Cocoanut  oil 

20°,         28° 
20°,         28° 

Non-drying 
^on-drying 

Butter  fat 
Nutmeg  oil 

29°,      35° 

Non-drying 
Von-drying 

Palmitin              

62° 

Palm  oil 

27°,      42° 

Non-drving 

Lard 
Butter  fat 
Cocoa  butter 
Human  fat 

28°,      45° 
29°,      35° 
30°,      34° 

^on-drying 
Non-drying 
Non-drying 
Non-drying 

Stearin  

55° 

Tallow 

36°,      49° 

Non-drying 

Lard 
Butter  fat 
Human  fat 

28°,      45° 
29°,   .  35° 

Non-drying 
Non-drying 
Non-d  rying 

Arachidin  

Unsaturated  Series 
HvDoffsein 

Peanut  oil 
Maize  oil 
Olive  oil 

Peanut  oil 

-   5° 

-20°,    -10° 

+  4°,  -   6° 

—     c° 

Sl.-drying 
Sl.-drying 
Non-drying 

SI  -drying 

Olein 

liquid 

Olive  oil  ! 

+  4°    -   6° 

Non-d  rying 

Cotton-seed  oil 
Lard 
Butter  fat 
Human  fat 

+           O                          O 
I    ,    —  IO 

28°,      45° 
29°,      35° 

Sl.-drying 
Non-drying 
Non-drying 
Non-drying 

Linolein  

liquid 

Linseed  oil 

-20°,    -27° 

Drying 

Linolenin     

liquid 

Poppy  oil 
Peanut  oil 
Olive  oil 
Linseed  oil 

-18° 

+  4°,  ~   6° 

-20°     -27° 

Drying 
Sl.-drying 
Non-drying 
Drving 

Iso-linolenin  

liquic 

Hemp  oil 
Poppy  oil 

-I5°,    -28° 

-18° 

Drying 
Drying 

FATS    AND    OILS 
AND  FATTY  ACIDS 


209 


Acid 

M.P. 

B.P. 

Solubility 
in  water 

Volatility 

Reaction  with 
Halogens 

Saturated  Series 

Butyric,  C3H7—  COOH.  .  .  . 

-2° 

162° 

Soluble 

Vol.  285° 

No  reaction 

Caproic   C5HuCOOH 

-i   5° 

235° 

Insol. 

No  reaction 

Caprylic,  C7Hi5COOH  

*  *  o 

16.5° 

O  3 

236° 

Sol.  hot 

No  reaction 

Capric,  C9H19—  COOH.  .  .  . 

o 

30° 

O  w 

268° 

Sh-sol. 



No  reaction 

Laurie,  CUH23COOH  

43° 

225° 

Insol. 

Vol.  steam 

No  reaction 

Myristic,  CisH^COOH.  .  .  . 

T^O 

53-8° 

196° 

Insol. 

Sl.-vol. 

No  reaction 

(15  mm.) 

Palmitic,  Ci5H3iCOOH.  .  .  . 

62° 

339° 

Insol. 

Non-vol. 

No  reaction 

Stearic,  C1VH35COOH  

69.2° 

359° 

Insol. 

Non-vol. 

No  reaction 

Arachidic,  Ci9H39COOH.  .  . 

75° 

Insol. 

Non-vol. 

No  reaction 

Unsalnrated  Series 

Hypogaeic,  Ci5H29COOH  .  . 

33° 

Insol. 

Non-vol. 

Adds  2Br 

Oleic,  Ci7H33COOH 

14° 

250° 

Insol. 

Vol.  250° 

Adds  2Br 

Linoleic,  Ci7H3iCOOH 

x  *T 

liquid 

*  ow 

Insol. 

Non-vol. 

Adds  4Br 

at  —  18° 

Linolenic,  Ci7H29COOH..  . 
Iso-Hnolenic,  C17H29COOH 

>  liquic 

Insol. 

Non-vol. 

Adds  6Br 

14 


2IO 


ORGANIC  CHEMISTRY 


regard  to  these  analytical  reactions  and  the  methods  for  their  applica- 
tion  such  books  as,  Lewkowitsch,  "Fats,  Oils  and  Waxes,"  may  be 
consulted. 

Physical  Constants       t 

Specific  Gravity. — The  physical  constants  of  fats  and  oils  are  often 
used  for  purposes  of  identification.  Those  most  commonly  used  are, 
specific  gravity,  melting  point  or  solidification  point,  refractive  index  and 
viscosity.  The  specific  gravity  may  be  most  readily  determined,  in 
the  case  of  oils  or  easily  melting  fats  by  means  of  an  immersion  hydro- 
meter. It  may  also  be  determined  more  accurately  by  use  of  a  specific 
gravity  bottle  or  picnometer.  The  specific  gravity  of  some  oils  may 
be  cited  as  follows: 


Oil 

Sp.  Gr. 

Oil 

Sp.  Gr. 

Olive  oil.  

o.oi  s  (at  i  c;0) 

Linseed  oil  (boiled) 

o  04^  (at  i  s°) 

Almond  oil 

o  017  (at  i<?°) 

Palm  oil 

O    Q32 

Peanut  oil  

o.oio  (at  i<°) 

Cocoa  butter  

o  060 

Cotton  seed  oil    .   . 

o  Q2i  (at  iq°) 

Cod  liver  oil 

o  926 

Sun-flower  oil  

0.925  (at  15°) 

Butter  fat  

0.868  (at  100°) 

Poppy  seed  oil  

o  926  (at  15°) 

Lard     ,  

o  859  (at  100°) 

Hemp  seed  oil  

0.928  (at  15°) 

Tallow  

0.857  (at  100°) 

Linseed  oil  (raw)  

0.934  (at  15°) 

Cocoanut  oil  

0.871  (at  100°) 

Melting  Point,  Titer. — The  melting  point  of  fats  and  oils  is  deter- 
mined by  means  of  simple  apparatus  similar  to  that  used  in  determining 
the  melting  point  of  organic  compounds.  In  many  cases  the  tempera- 
ture at  which  the  melted  fat  or  liquid  oil  solidifies  is  determined,  and 
this  is  called  the  solidification  point.  As  there  is  considerable  variation 
in  the  melting  point  or  solidification  point  of  most  fats  it  has  been  found 
that  the  solidification  point  of  the  mixed  free  acids  is  a  better  constant. 
The  fat  is  saponified  and  then  the  acids  are  set  free  by  acidifying  the 
saponification  liquid.  The  solidification  point  of  the  mixed  acids  is 
then  determined.  This  solidification  point  is  known  as  the  liter.  The 
more  common  fats  melt  at  temperatures  ranging  from  20°  to  49°,  co- 
coanut  oil  being  the  most  liquid  and  tallow  the  most  solid.  Of  the 
oils,  linseed  oil  is  the  most  difficultly  solidified,  at  —20°  to  —27°,  while 
olive  oil  is  the  most  easily  solidified,  at  +4°  to  —6°. 


FATS    AND    OILS 


211 


Fat                       1 

M.P. 

Oil 

S.P. 

Tallow        

36°-4Q° 

Olive  oil  

+  4°  to  -  6° 

Lard 

28°-4->° 

Peanut  oil 

-     c° 

Laurel  oil  

32°-36° 

Cotton  seed  oil  

+   i°  to  -10° 

Palm  oil 

27°-42° 

Almond  oil  

—  10°  to    —20° 

Butter  fat  

29°-35° 

Sun-flower  oil  

-15°  to  —  18° 

Cocoa  butter  
Cocoanut  oil 

3°°-34° 

20°-28° 

Poppy  seed  oil  
Hemp  seed  oil  . 

-18° 
—  15°  to  —28° 

Linseed  oil  

-20°  tO    -27° 

Table  XV  shows  that  when  the  melting  point  of  the  principal  ester 
present  in  an  oil  is  known  the  melting  point  of  the  fat  is  considerably 
lower.  This  is  due  to  the  fact  that  in  these  fats  a  considerable 
quantity  of  olein  is  also  present  which  lowers  the  melting  point.  On 
account  of  the  properties  of  palmitin  and  stearin,  on  the  one  hand, 
and  of  olein  and  the  other  unsaturated  esters,  on  the  other,  it  may 
be  said,  in  general,  that  the  larger  the  proportion  of  the  former,  which 
is  present  in  a  fat,  the  more  solid  will  the  fat  be,  while,  if  the  propor- 
tion of  olein  is  larger  the  fat  will  be  more  liquid  in  character.  It  will  be 
observed,  also,  that  there  is  considerable  range  between  the  minimum 
and  maximum  figures,  both  in  the  case  of  the  specific  gravity  and  also 
of  the  melting  point.  This  is  readily  understood  when  we  consider 
the  nature  of  the  fats  and  oils  as  mixed  bodies,  more  or  less  variable 
in  the  condition  in  which  they  are  obtained  from  their  natural  sources. 

Refractive  Index,  Refractometers. — The  refractive  index  of  a  fat 
or  oil  is  the  angle  through  which  light  is  bent  or  refracted  by  passing 
through  a  thin  film  of  the  oil.  The  physical  instrument  which  is  used 
in  measuring  this  angle  is  called  a  refractometer.  The  instrument  is  so 
constructed  that  a  drop  of  oil  is  spread  as  a  film  between  two  prisms  and 
the  light  passes  through  this  film  into  the  eye  piece  of  the  instrument. 
With  oils  which  are  liquid  at  ordinary  temperatures  no  temperature 
controlling  device  is  necessary  but  with  fats  it  is  necessary  to  have  the 
prisms  surrounded  by  a  jacket  containing  water  at  a  raised  tempera- 
ture. The  most  universal  type  of  such  an  instrument  either  plain  or 
jacketed  is  the  Abbe  or  Abbe-Zeiss  refractometer.  On  this  instrument 
the  scale  reads  the  index  of  the  refraction  directly.  A  modified  form  of 
such  a  refractometer  devised  for  use  especially  with  butter  is  known  as 
the  butyro-refractometer.  On  this  instrument  the  scale  is  in  arbitrary 


212  ORGANIC  CHEMISTRY 

units  covering  the  range  of  butter,  lard  and  their  substitutes.  Another 
form  of  instrument,  the  oleo-refractometer,  measures  the  comparative 
refraction  of  two  oils  at  the  same  time  the  light  passing  through  two 
small  cylinders  filled  with  oil  one  being  a  pure  known  oil  as  standard 
and  the  other  an  unknown  oil  for  comparison.  Still  another  modifi- 
tion  is  one  known  as  the  immersion  refractometer.  As  its  name  indi- 
cates it  is  used  by  immersion  in  the  liquid  under  examination.  It  has 
the  advantage  of  being  able  to  be  used  not  only  with  emulsions  of 
fats,  but  also  to  determine  the  strength  of  a  large  variety  of  solutions 
such  as;  milk  serum  (whey);  acid,  alkali  and  salt  reagents;  alcohol; 
sugar  solutions,  etc.  The  scale  on  this  refractometer  is  also  arbitrary 
but  the  readings  may  be  readily  converted  into  refractive  indices  by 
the  use  of  tables. 

Viscosity. — The  viscosity  of  a  melted  fat  or  an  oil  may  be  defined 
as  the  friction  which  the  particles  exert  upon  each  other  in  moving. 
It  is  usually  determined  by  observing  the  flow  of  the  oil  through  a  capil- 
lary tube.  The  specific  viscosity  of  an  oil  is  the  rate  of  flow  compared 
with  water,  but  in  practice  the  viscosity  is  usually  compared  with  that  of 
some  oil  which  has  been  taken  as  a  standard.  The  oil  commonly  used  • 
as  such  a  standard  is  rape  oil.  In  this  case  the  viscosity  of  the  rape  oil 
is  considered  as  100. 

Chemical  Constants 

Saponification  Number,  Koetstorffer  Value. — When  an  ester  is 
saponified  the  reaction  is  quantitative.     In  the  case  of  a  pure  glycerol 
ester,  e.g.,  glyceryl  tri-palmitate,  saponification  is  in  accordance  with 
the  following  reaction: 
CH2— OOC— Ci5H3i  CH2— OH 

I  I 

CH— OOC— Ci5H3i  +  3K— OH  — •>  CH— OH  +  3Ci5H3i— COOK 

I  Potassium  Potassium  palmitate 

hydroxide   . 

CH2 — OOC — CisHsi        3  x  56.1)  CH2 — OH 

Glyceryl  tri-palmitate  Glycerol 

(mol.  wt.  =  806) 

From  the  molecular  weights  of  806  for  glyceryl  tri-palmitate  and  of 
56.1  for  potassium  hydroxide,  the  mass  proportions  are: 

Glyceryl  tri-palmitate:  Potassium  hydroxide:  :  806  :  168.3 
Taking  the  mass  of  glyceryl  tri-palmitate  as  i.oo  the  mass  of  po- 
tassium hydroxide  becomes  0.2088.     That  is,  to  saponify  i.oo  gm.  of 
pure  ester  will  require  0.2088  gm.  of  potassium  hydroxide.     Expressing 


FATS   AND    OILS 


213 


this  in  milligrams  we  have  208.8  which  represents  the  number  of  milli- 
grams of  potassium  hydroxide  required  to  saponify  i.oo  gm.  of  the  fat. 
This  number  is  known  as  the  saponification  number  or  saponification 
•value  which  may  be  denned  as  just  stated.  It  is  also  known  as  the 
Koetstorjfer  Value,  from  the  name  the  man  of  who  devised  it.  In  prac- 

N 

tice  the  saponification  of  a  fat  is  effected  by  using  a  Normal,  — ,  po- 
tassium hydroxide  solution  which  contains,  in  i.oo  cc.  0.0561  gm.  or 

56.1  m.  gm.  of  potassium  hydroxide.     If,  then,  for  any  weight  of  fat 

N 

taken,  the  number  of  cubic  centimeters  of  —  KOH  required  is  multi- 
plied by  56.1  and  the  product  divided  by  the  number  of  grams  of  fat, 
the  result  will  be  the  saponification  value,  i.e.; 


Saponification  Value 


cc.         KOH  X  56.1 


Weight  of  fat  in  grams 

The  saponification  values  of  a  few  of  the  pure  esters  and  a  few 
fats  and  oils  are: 


Esters 

Sap.  Val. 

Fats 

Sap.  Val. 

Butyrin  
Palmitin 

557-3 
208  8 

Butter  fat  
Palm  oil. 

227.0 
196    O~2O2 

Lard  

lof  4 

Stearin.  ...        

180  i 

Beef  tallow  . 

IQ-J    2—  2OO 

Olein 

IQO    4 

Olive  oil 

185  o~io6 

Linolein  

191.7 

Linseed  oil  

192.0-195 

Bromine  or  Iodine  Value,  Hiibl-Wijs. — Another  important  chemi- 
cal constant  of  fats  and  oils  is  one  which  depends  upon  the  nature  of 
the  acid  present  as  an  ester.  The  acids  present  as  esters  in  fats  and 
oils  are  of  two  different  classes,  viz.,  those^belonging  to  the  saturated 
series  and  those  belonging  to  the  unsaturated  series.  We  have  shown 
that  the  distinguishing  reaction  of  these  two  series  of  compounds,  both 
in  the  hydrocarbons  and  the  various  classes  of  their  derivatives,  is, 
that  unsaturated  compounds  take  up  halogen  directly  with  the  formation 
of  addition  products.  It  has  been  found  that  the  glycerol  esters  of  the 
unsaturated  acids  form  addition  products  readily,  under  certain  condi- 
tions. If,  therefore,  a  fat  takes  up  bromine  or  iodine  directly  an  ester 
of  an  unsaturated  acid  must  be  present.  The  determination  of  the 


214  ORGANIC  CHEMISTRY 

amount  of  halogen  thus  taken  up  will  show  us  the  amount  of  the  un- 
saturated  ester  provided  that  we  know  which  particular  acid  is  repre- 
sented. The  unsaturated  acids  which  occur  as  esters  in  fats  and  oils 
as  has  been  previously  stated,  belong  to  three  groups,  viz.,  the  oleic 
acid  group,  (CnH2n_2)O2,  the  linoleic  acid  group,  (CnH2n-4)O2,  and  the 
linolenic  acid  group,  (CnH2n_6)O2  (p.  181).  The  amount  of  halogen 
taken  up,  in  the  formation  of  addition  products,  depends  upon  the 
amount  of  the  unsaturation,  i.e.,  the  number  of  double  or  triple  bonds, 
as  indicated  by  the  lower  hydrogen  content.  Oleic  acid,  with  one 
double  bond,  takes  up  two  halogen  atoms  (bromine  or  iodine)  per  mole- 
cule of  the  acid.  Linoleic  acid,  with  two  double  bonds  takes  up  four 
halogen  atoms  per  molecule  and  linolenic  acid,  with  three  double  bonds, 
takes  up  six  halogen  atoms  per  molecule.  The  esters,  tri-olein,  tri- 
linolein,  and  tri-linolenin,  being  tri-acid  esters,  will,  of  course,  take  up, 
per  molecule,  three  times  as  much  halogen  as  given  above  for  the  corre- 
sponding acid.  According  to  the  following  proportions  the  amount  of 
iodine  theoretically  absorbed  by  the  three  most  common  unsaturated 
acids  may  be  readily  calculated,  as  follows: 

Ci7H33  -  COOH  :  21  :  :  282  :  2  X  127  :  :  100  :    90.07 

Oleic  acid 

Ci7H3i  -  COOH  :  41  :  :  280  : 4  X  127  :  :  100  :  181.42 

Linoleic  acid 

Ci7H29  -  COOH  :  61  :  :  278  :  6  X  127  :  :  100  :  274.1 

Linolenic  acid 

Therefore,  the  amount  of  iodine,  in  grams,  absorbed  by  100  grams  of 
the  acid,  is,  for  these  three  acids,  respectively,  90.07,  181.42,  274.1. 
These  numbers  are  known  as  the  iodine  values,  also  as,  the  Hiibl,  or 
Wijs  numbers,  from  the  names  of  men  who  devised  the  two  most 
accurate  methods  of  determination.  In  practice,  iodine  is  used  more 
often  than  bromine.  The  form  in  which  the  iodine  is  used  is  that  of 
iodine  mono-chloride,  Id,  or  iodine  tri-chloride,  IC13.  The  first  is 
made  by  mixing  a  solution  of  iodine  and  mercuric  chloride, 

HgCl2  +  I2      >       HgCII  +  IC1  Iodine  mono-chloride,  (Hiibl). 

The  iodine  tri-chloride  solution  is  made  by  the  addition  of  chlorine  to 
an  iodine  solution, 

I2  +  3C12     >     2IC13         Iodine  tri-chloride,  (Wijs). 

The  iodine  mono-chloride  solution  is  the  Hiibl  solution,  the  iodine  tri- 
chloride solution,  is  the  Wijs  solution.  In  either  case,  the  exact 


FATS   AND    OILS 


215 


strength  of  the  solution,  in  terms  of  iodine,  is  determined  by  titration. 
The  iodine  solution  is  added  to  the  fat  or  acid  dissolved  in  chloroform 
or  carbon  tetra-chloride,  and  the  absorption  allowed  to  take  place. 
After  the  absorption  is  completed  the  excess  of  iodine  is  determined 
by  titration  and  the  amount  actually  absorbed  is  calculated  per  100 
grams  of  the  fat  or  acid  used.  The  iodine  values,  as  thus  determined,  for 
some  of  the  common  fats  and  oils  are  given  in  the  following  table.  It 
will  be  noticed  that,  with  the  exception  of  cocoanut  oil  and  cocoa 
butter,  butter  fat  has  the  lowest  value  of  the  common  fats  and  oils. 


Fat  or  oil 

Iodine    value 

Fat  or  oil 

Iodine    value 

Linseed  oil 

177—201 

Laurel  oil 

68  0-80  o 

Hemp  seed  oil  

148 

Palm  oil  

ci  .  e 

Poppv  seed  oil  . 

133—143 

Cocoa  butter 

22    0—4.  T    O 

Sun-flower  oil 

1  1  Q—  1  3  ? 

Cocoanut  oil 

8  o—  o  ^ 

Maize  oil  

1  1  1  —  130 

Human  fat.  .        .    

s8   Q—  73.3 

Cotton  seed  oil 

i  08—  i  10 

Lard 

CO   O~7O    O 

Almond  oil  

Q3—    Q7 

Beef  tallow  

38  .  0—46  .  o 

Peanut  oil 

83—IOO 

Butter  fat         .    . 

26  0—38  o 

Olive  oil  

79-  88 

Insoluble  Acids,  Hehner  Value. — The  acids  which  are  set  free  from 
the  fat  or  oil  by  saponification  and  subsequent  acidification,  differ  in 
two  other  respects  as  well  as  in  their  power  to  absorb  halogens.  These 
are,  (i)  solubility,  (2)  volatility.  -  Some  of  the  acids,  like  butyric,  are 
soluble  in  water  while  most  of  them  are  insoluble.  Some,  like  butyric 
and  lauric,  are  volatile  with  steam,  others  are  non-volatile.  The  deter- 
mination of  the  amount  of  insoluble  acids  in  a  fat  gives  us  a  value  known 
as  the  Hehner  Value  which  may  be  defined  as  the  sum  of  the  insoluble 
acids  and  unsaponifiable  matter  in  a  fat  expressed  in  per  cent.  After 
saponification  of  the  fat  the  soap  solution  is  acidified  and  the  insoluble 
fatty  acids  are  collected  on  a  filter  paper  and  weighed.  In  the  case  of 
most  of  the  common  fats  and  oils  the  Hehner  value  lies  in  the  neighbor- 
hood of  95,  with  butter  fat  as  the  striking  exception,  with  a  value  of 
less  than  90.  The  Hehner  values  which  differ  much  from  95  are  given 
in  the  table  at  the  end  of  this  section. 

Volatile  Acids  or  Reichert-Meissl  Value. — The  separation  of  the 
volatile  from  the  non-volatile  acids  is  accomplished  by  distillation  of 
the  mixed  fatty  acids  after  they  have  been  set  free  from  the  saponifica- 


216 


ORGANIC  CHEMISTRY 


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HIGHER   POLY-HYDROXY   ALCOHOLS  217 

tion  liquid  by  acidifying.  The  Reichert-Meissl  Value  may  be  defined 
as,  the  number  of  cubic  centimeters  of  one-tenth  normal  potassium  hydrox- 
ide required  to  neutralize  the  volatile  fatty  acids,  obtained  from  3.0  grams 
of  a  fat  or  oil  by  the  Reichert  distillation  process.  This  determination 
does  not  yield  absolute  values  but  is  of  considerable  importance,  especi- 
ally in  the  examination  of  butter  and  its  imitations.  Some  of  the 
values  which  have  been  obtained,  will  be  found  in  the  table  preceding. 
It  will  be  seen  that  butter  fat  alone  has  a  value  which  is  at  all  high.  This 
is  natural  as  it  is  the  only  one  which  has  a  large  amount  of  butyric" 
acid.  The  composition  of  butter  fat  may  be  given  in  this  connection. 
As  recently  determined  by  E.  B.  Holland  of  the  Massachusetts  Experi- 
ment Station,  the  acids  present  are  as  follows.  (Mass.  Exp.  Sta.  BuL, 
166;  1915). 

COMPOSITION  OF  BUTTER  FAT 

Volatile  Acids  Non-volatile  Acids 

Butyric 3.2  per  cent.    Laurie 1.9  per  cent. 

Caproic 1.4  per  cent.     Myristic 22.6  per  cent. 

Caprylic i  .o  per  cent.     Palmitic 19 .3  per  cent. 

Capric 1.8  per  cent.     Stearic 11.4  per  cent. 

Oleic 27.4  per  cent. 

C.  HIGHER  POLY-HYDROXY  ALCOHOLS 

The  di-hydroxy  and  the  tri-hydroxy  derivatives  of  the  saturated 
hydrocarbons  which  have  been  studied  thus  far  are: 
CH2— OH  CH2— OH 

I  | 

CH2— OH  .  CH  —OH 

Ethylene  glycol  I 

Ethan-di-ol 

CH2— OH 

Glycerol 
Propan-tri-ol 

As  previously  stated,  it  is  generally  true  that  stable  compounds  do 
not  result  when  more  than  one  hydroxyl  group  is  linked  to  one  carbon 
atom.  It  is  plain  therefore  that  the  simplest  member  of  each  class 
of  poly-hydroxy  substitution  products  must  have  as  many  carbon  atoms 
as  there  are  hydroxyl  groups.  Thus,  the  simplest  di-hydroxy  com- 
pound is  the  di-hydroxy  ethane,  glycol,  and  similarly,  the  simplest 
tri-hydroxy  compound  is  the  tri-hydroxy  propane,  or  glycerol,  as 
above.  Considering,  now,  those  poly-hydroxy  substitution  products 


2l8  ORGANIC  CHEMISTRY 

which  contain  more  than  three  hydroxyl  groups,  we  find  that  com- 
pounds are  known  with  four,  five,  six,  seven,  eight,  and  nine.  These 
compounds  all  agree  with  the  statements  just  made  and  the  constitu- 
tion of  each  has  been  fully  established.  In  connection  with  them, 
two  general  facts  are  of  importance.  First,  they  are  all  true  alcohols, 
being  a  combination  of  primary  and  secondary  alcohols,  as  has  been 
explained  under  glycerol.  When  oxidized,  therefore,  two  different 
series  of  compounds  are  possible.  The  primary  alcohol  groups,  which 
are  always  the  end  carbon  groups,  are  oxidizable  to  aldehyde  and  then 
to  acid  groups.  The  secondary  alcohol  groups  which  include  all  of 
the  intermediate  carbon  groups,  are  oxidizable  to  ketone  groups  (p. 
121).  The  oxidation  products  of  these  poly-hydroxy  alcohols  lead 
directly  to  the  very  important  group  of  compounds  known  as  the 
carbohydrates,  or  sugars,  to  be  studied  later.  As  was  mentioned,  in 
connection  with  glycol  and  glycerol,  the  increased  substitution  of  the 
hydroxyl  group  into  a  hydro-carbon  chain,  confers  upon  the  compound  a 
sweet  taste.  The  compounds  following,  viz.,  erythritol,  arabitol, 
mannitol,  etc.,  all  possess  a  sweet  taste.  Second,  the  second  general 
fact  is,  that  in  all  of  these  higher  hydroxy  compounds  we  have  more 
than  one  asymmetric  carbon  atom,  as  indicated  by  the  *  in  the  formulas. 
This  makes  possible  the  existence  of  these  compounds  in  several 
stereo-isomeric  forms,  which  will  be  discussed  at  length  when  we  consider 
the  carbohydrates. 

Erythritol,  CH2(OH)— CH(OH)— CH(OH)— CH2(OH) 

The  tetra-hydroxy  compound,  viz.,  tetra -hydroxy  butane,  or 
i-2-3-4-butan-tetr-ol,  is  known  as  erythritol  or  erythrite.  It  occurs 
free  in  nature  in  certain  algae  and  also  as  erythrin,  an  ester  of  an  aro- 
matic acid,  in  certain  lichens.  It  is  a  crystalline  substance,  melting 
at  126°  and  boiling  at  329°.  It  is  easily  soluble  in  water  and  slightly 
in  alcohol. 

Arabitol,Xylitol,Rhamnitol,CH2(OH)— CH(OH)— CH(OH)— CH(OH)— CH2(OH) 

The  penta-hydroxy  compound,  viz.,  penta -hydroxy  pentane,  or  1-2- 
3-4-5-pentan-pent-ol,  is  known  as  arabitol  or  arabite.  It  occurs  also 
in  stereo-isomeric  forms  as  xylitol,  and  rhamnitol.  The  formula  is  as 
above.  The  names  of  these  three  isomers  are  derived  from  the  sub- 
stances or  compounds  from  which  they  are  obtained.  Arabitol  is 
obtained  from  arabinose  which  is  found  in  gum  ara  bic.  Xylitol  is 


HIGHER   POLY-HYDROXY   ALCOHOLS  219 

similarly  related  to  xylite,  a  woody  cellulose,  and  rhamnitol  to  rhamnose 
a  sugar.  The  first  of  these  melts  at  102°,  the  second  has  not  been  crys- 
tallized and  the  third  melts  at  121°.  They  are  all  soluble  in  water. 

Mannitol,  Dulcitol,  Sorbitol 

CH2(OH)— CH(OH)— CH(OH)— CH(OH)— CH(OH)— CH2(OH) 

*  *  *  * 

The  hexa-hydroxy  compound,  viz.,  hexa-hydroxy  hexane,  or  1-2-3 - 
4-5-6-hexan-  hex-ol,  with  the  formula  as  above,  exists  in  different  stereo- 
isomeric  forms,  the  three  most  common  ones  being  known  as  mannitol 
or  mannite,  dulcitol  or  dulcite,  and  sorbitol  or  sorbite.  Mannitol  is 
found  quite  widely  distributed  in  nature.  Its  chief  source  is  the  juice 
of  the  manna  ash  tree  (Fraxinus  Ornus) .  The  juice  is  dried  or  coagu- 
lated and  the  residue,  known  as  manna,  yields  about  30-60  per  cent,  of 
mannitol.  The  manna  is  sweet  and  edible.  This  manna  is  not  the  one 
mentioned  in  the  Bible  as  that  was  probably  an  edible  lichen  (Sphaero- 
thallia  esculenta),  which  grows  upon  a  tammarix  tree  (Tammerix 
gallica,  var.  mannifera).  This  last  manna  contains  a  sugar,  but  no  man- 
nitol. Mannitol  is  also  found  in  a  toad-stool  (Agaricus  integer),  and 
amounts  to  about  20  per  cent,  of  the  dry  substance.  It  is  present  in 
small  amounts  in  celery,  syringa  leaves,  olives,  etc.  It  also  occurs  in 
rye  bread.  From  water  mannitol  crystallizes  in  prisms  but  from  alcohol 
in  needles.  It  is  soluble  in  six  parts  of  water.  It  melts  at  165°  and  in 
water  solution  it  is  levo  rotatory.  The  synthesis  of  mannitol  involves 
its  relation  to  the  sugars  and  will  not  be  considered  at  this  time.  The 
same  is  true  in  regard  to  the  oxidation  products.  The  other  two  hexa- 
hydroxy  alcohols,  mentioned  above,  are  stereo-isomeric  with  mannitol. 
They  resemble  it  in  chemical  properties  differing  from  it  physically, 
especially  in  optical  properties.  Dulcitol,  is  inactive,  while  sorbitol  is 
levo  rotatory  like  mannitol.  The  different  stereo-chemical  structures 
for  these,  and  the  other  isomeric  hexa-hydroxy  alcohols,  will  be 
explained  when  the  stereo-isomerism  of  the  carbohydrates  is  considered. 
Suffice  it  to  say  at  this  time  that  there  are  possible  ten  isomeric 
compounds  of  the  same  structure  as  mannitol.  Dulcitol  is  found  in 
nature  in  a  manna  from  Madagascar  and  in  some  plants.  It  crystal- 
lizes in  columns  which  melt  at  188.5°.  It  is  less  soluble  in  water  than 
mannitol.  Sorbitol  is  found  in  the  berries  of  the  mountain  ash  tree, 
in  pears,  plums,  cherries,  apples,  etc.  It  crystallizes  from  water  in  fine 
needles  which  melt  at  iio°-iii°. 


VIII.  MIXED  POLY-SUBSTITUTION  PRODUCTS 
GENERAL 

Thus  far,  in  considering  the  poly-substitution  products,  resulting 
from  the  substitution  of  more  than  one  mono-valent  element  or  radical 
for  an  equivalent  number  of  hydrogen  atoms,  we  have  spoken  of  those 
compounds  in  which  the  two  or  more  substituting  groups  are  the  same, 
viz.,  poly-halogen  compounds,  poly-alcohols,  poly-amines,  etc.  Hav- 
ing just  considered  the  poly-alcohols  it  would  seem  natural  that  the  next 
step  would  be  to  study  similar  compounds  containing  more  than  one 
aldehyde  or  acid  group,  i.e.,  poly-aldehydes  and  poly-acids.  Before 
we  take  up  these  last  two  groups  of  compounds,  however,  it  seems  better 
to  consider,  those  poly-substitution  products  in  which  the  substitut- 
ing groups  are  different.  It  is  plain  that  a  great  variety  of  mixed  com- 
pounds are  possible  as,  theoretically,  we  may  have  any  combination  of 
two  or  more  different  substituting  elements  or  groups  which  are  capable 
of  forming  substitution  products.  In  many  cases  of  compounds  which 
are  not  important  we  shall  simply  give  their  formulas  and  names  as 
examples  without  further  description. 

A.  MIXED  HALOGEN  AND  CYANOGEN  COMPOUNDS 

Halogens  Only. — In  the  group  of  mixed  poly-halogen  compounds 
we  may  have  di-substitution  products  like  di-chlor  methane,  CH2C12, 
such  as  CH2ClBr,  brom  chlor  methane,  CH2BrI,  brom  iodo  methane, 
etc.;  tri-substitution  products  like  chloroform,  CHC13,  e.g.,  CHCl2Br, 
brom  di-chlor  methane,  CHClBr2,  di-brom  chlor  methane,  CHC12I, 
di-chlor  iodo  methane  etc.,  and  tetra-substitution  products  like  car- 
bon tetra-chloride,  CC14,  such  as  CC12I2,  di-chlor  di-iodo  methane, 
etc.  These  are  all  derivatives  of  methane  but  analogous  derivatives 
of  other  hydrocarbons  are  known. 

Halogen  and  Nitro  Group. — Chlor  Picrin. — We  may  also  have  mixed 
compounds  containing  halogen  elements  and  some  non-halogen  element 
or  group  such  as  the  nitro  group.  An  example  of  this  is  chlor  picrin 
so  named  because  it  is  made  by  the  chlorination  of  picric  acid,  a  benzene 

220 


MIXED    POLY-SUBSTITUTION   PRODUCTS  221 

compound  (Pt.  II).  Its  formula  is  CC13(NO2).  It  is  thus  related  to 
chloroform  and  is  known  also  as  nitro  chloroform.  It  is  a  liquid,  b.p. 
112°,  with  an  extremely  bad  odor  and  a  very  irritating  action  upon 
eyes  and  mucous  membranes.  It  is  one  of  the  so-called  war  gases  and 
was  one  of  two  or  three  most  extensively  used  in  the  late  war. 

Halogens  and  Amino  Group. — Mixed  compounds  containing  both 
halogens  and  amino  groups  may  be  illustrated  by  the  following:  CH2- 
Br — CH2 — NH2,  i-amino  2-brom  ethane,  CH3 — CI2 — NH2,  i -amino 
i-di-iodo  ethane,  H2N— CH2— CHC1— CH2— NH2,  2-chlor,  i-3-di- 
amino  propane. 

Halogens  and  Cyanogen  Group. — Compounds  containing  both  halo- 
gens and  the  cyanogen  group  are  nitrites  of  halogen  acids.  They  may  be 
considered  as  derivatives  of  hydrogen  cyanide,  H — CN,  or  of  cyanogen, 
NC — CN.  The  simplest  compounds  of  this  kind  contain  no  other 
carbon  than  the  cyanogen  carbon,  e.g.,  chlor  cyanogen,  Cl — CN,  brom 
cyanogen,  Br — CN,  and  iodo  cyanogen,  I — CN.  These  are  nitriles 
of  the  corresponding  halogen  formic  acids.  Halogen  derivatives  of 
alkyl  cyanides  may  be  illustrated  with  those  related  to  methyl  cyanide 
or  acetic  nitrile,  CH3— CN. 

CH2C1— CN  CHC12— CN  CC13— CN 

Chlor  methyl  cyanide       Di-chlor  methyl  cyanide      Tri -chlor  methyl  cyanide 
Chlor  acetic  nitrile  Di-chlor  acetic  nitrile  Tri-chlor  acetic  nitrile 

Cyanogen  and  Amino  Compounds. — Cyan -amide. — As  derivatives 
also  of  hydrogen  cyanide  or  of  cyanogen  and  likewise  as  derivatives  of 
ammonia  or  of  amines  are  compounds  containing  both  a  cyanogen  and 
an  amino  group.  The  most  important  representative  of  this  kind  is  a 
compound  known  as  cyan-amide,  NC — NH2.  This  compound  will  be 
considered  later  with  other  cyanogen  compounds  (p.  422).  Analogous 
to  cyan-amide  are  corresponding  alkyl  amino  compounds,  e.g., 
cyan  methylamine,  NC— NH(CH3),  and  cyan  di -ethyl  amine 
NC— N(C2H5)2. 

In  all  of  these  mixed  compounds,  the  substances  possess  the  prop- 
erties of  both  kinds  of  substitution  products  represented.  The  halogen 
nitro  compounds,  on  reduction,  yield  halogen  amines.  The  halogen 
amines  are  basic  compounds,  like  the  amines  themselves,  and  form  salts 
with  mineral  acids.  The  halogen  cyanogen  compounds  possess  the 
nitrile  properties  of  alkyl  cyanides,  and  on  hydrolysis  yield  halogen 
acids.  The  cyanogen  amines  are,  similarly,  both  acid  nitriles  and 


222  ORGANIC  CHEMISTRY 

amine  bases.  Thus  we  could  expand  this  class  of  compounds  almost 
indefinitely,  but  that  is  unnecessary,  in  our  present  study.  Any  par- 
ticular compound  which  is  of  importance,  in  connection  with  other 
compounds,  will  be  taken  up  in  the  proper  place. 


B.  MIXED  HYDROXY  COMPOUNDS—  SUBSTITUTED 
ALCOHOLS 

I.  HALOGEN  -ALCOHOLS 

The  most  important  derivatives  of  this  mixed  type  are  those  ob- 
tained by  substituting,  in  alcohols,  aldehydes,  or  acids,  some  other 
element  or  group.  This  gives  us  compounds  known,  in  general, 
as  substituted  alcohols,  substituted  aldehydes,  and  substituted  acids.  These 
three  classes  of  mixed  compounds  will  now  be  considered.  The  simplest 
group  of  substituted  alcohols  are  the  halogen  alcohols.  Of  the  halo- 
gen alcohols  the  simplest  would  be  derived  from  methyl  alcohol,  e.g., 

CH3—  OH  -  »CH2C1—  OH 

Such  a  compound,  however,  if  produced  by  the  action  of  chlorine  upon 
methyl  alcohol,  evidently  splits  off  hydrochloric  acid  and  yields  an 
aldehyde,  as  follows: 

H  H  H 


H—  C—  OH  +  C12       —»    H—  C—  O(H     -HC1    H—  C  =  O 

--  >      Formaldehyde 

H  (Cl) 

Methyl  alcohol 

That  is,  the  action  of  chlorine,  in  such  cases,  is  simply  oxidation, 
through  loss  of  hydrogen,  the  alcohol  being  oxidized  to  an  aldehyde. 
The  reaction,  as  given  above,  does  not  take  place  with  methyl  alcohol, 
but  does  occur  in  the  case  of  ethyl  alcohol  when  it  is  treated  with  chlor- 
ine in  the  manufacture  of  chloroform  (p.  183).  In  general,  this  result 
is  always  obtained  when  alcohols  are  treated  with  halogens.  The 
carbon  group  affected  by  the  halogen  is  always  that  one  which  contains 
the  hydroxyl  group.  This  gives  a  carbon  group  having  both  a  halogen 
and  hydroxyl  present  in  it  and  such  a  grouping,  being,  evidently  un- 


MIXED    POLY-SUBSTITUTION   PRODUCTS  223 

stable,  breaks  down,  with  the  loss  of  hydrogen  chloride  and  an  aldehyde 
results. 

H  H  H 

—  HC1 

R— c— OH  +  cit     — >     R— c— O(H     _:;     R— c  =  o 

I  Aldehyde 

H  (Cl 

Primary  alcohol 

With  secondary  alcohols  the  action  is  similar,  the  resulting  com- 
pound being  the  oxidation  product  of  secondary  alcohols,  viz.,  a  ketone. 

R  R  R 

I  I  HP1  ' 

R— C— OH  +  C12  — >        R— C— O(H       __:        R— C  =  O 

|  Ketone 

H  (Cl 

Secondary  alcohol 

With  the  hydrochloric  acid  produced  in  this  reaction,  a  secondary 
reaction  sometimes  occurs,  between  the  alcohol  and  the  acid,  forming 
an  alkyl  halide  and  water,  as  follows : 

R  R 

I  I 

R— C— (OH  +  H)— Cl        >        R— C— Cl  +  H— OH 

H  H 

Alcohol  Alkyl  halide 

Halogen  Hydrines. — Another  type  of  halogen-alcohol  is  possible 
in  the  case  of  alcohols  containing  two  or  more  carbon  groups.  The 
halogen  may  enter  the  other  carbon  group  than  the  one  in  which  the 
hydroxyl  is  already  present,  e.g., 

CH3— CH2OH        >        CH2C1— CH2OH 

Ethyl  alcohol  Glycol  chlor  hydrine 

In  such  cases,  with  the  halogen  and  hydroxyl  linked  to  different  carbon 
atoms,  stable  compounds  result.  As  direct  action  of  halogens  oxidizes 
the  alcohol  to  aldehyde  or  ketone,  this  new  kind  of  halogen-alcohol 
must  be  prepared  by  a  different  reaction.  When  poly-hydroxy  alcohols 
react  with  halogen  acids,  e.g.,  hydrochloric  acid,  HC1,  or  with  phos- 


224  ORGANIC  CHEMISTRY 

phorus  halogen  compounds,  e.g.,  phosphorus  tri-chloride,  PC13,  or 
tri-bromide,  PBr3,  etc.,  one  of  the  hydroxyl  groups  is  replaced  by  a 
halogen  atom,  yielding  a  compound  known  as  a  halogen-hydrine. 
These  compounds  are  plainly  mono-esters  of  the  poly-hydroxy  alcohol 
and  the  halogen  acid  and  have  been  previously  referred  to  (p.  201). 

CH2OH  PC13  CH2C1 

+       or  -» 

CH2OH  HC1  CH2OH 

Glycol  Glycol  chlor  hydrine 

i-Chlor  2-hydroxy  ethane 

More  than  one  hydroxyl  may  be  thus  replaced  and  the  resulting  com- 
pounds are  known  as,  di-halogen  hydrines,  tri-halogen  hydrines,  etc., 
depending  upon  the  number  of  halogens  introduced.  The  compound 
given  above  is,  glycol  chlor  hydrine.  Considering  these  halogen- 
alcohol  compounds  as  derivatives  of  the  mono-hydroxy  alcohols  we 
have  other  known  compounds  in  which  more  than  one  halogen  is 
introduced  into  the  non-hydroxy  carbon  group,  e.g.', 

CHC12— CH2OH          and          CHC12— CH2— CH2OH 

i-i-Di-chlor    2-hydroxy  ethane  i-i-Di-chlor    3-hydroxy  propane 

From  the  higher  poly-hydroxy  alcohols  similar  halogen-alcohols 
are  obtained,  which  are  known,  also,  as  halogen-hydrines,  e.g. ; 

CH2— OH        CH2— Cl        CH2— Cl          CH2— OH        CH2— Cl 

!  I  I  I  I 

CH— OH         CH— OH      CH— OH        CH  — Cl  CH  — Cl 

I  I  I  I  I 

CH2— OH        CH2— OH       CH2— Cl         CH2— OH        CH2^-OH 

Glycerol  Glycerol  Glycerol  a-a-di-  Glycerol  Glycerol  a-0-di- 

i-2-3-Tri-hydroxy      a-chlor  hydrine  chlor  hydrine  /3-chlor-hydrine          -chlor  hydrine 

propane  i -Chlor  2-3-di-  i-3-Di-chlor  -2  2-Chlor  i-3-di-         i-2-Di-chlor  3- 

hydroxy  propane  hydroxy  propane  hydroxy  propane  -hydroxy  propane 

The  chlor-hydrines  are  especially  important  in  synthetic  reactions 
which  we  shall  use  later. 

Epi-chlor  Hydrines. — An  important  reaction  takes  place  with 
mono-chlor  hydrines  which  contain  at  least  two  remaining  hydroxyl 
groups,  as,  e.g.,  those  derived  from  glycerol.  The  mono-chlor  hydrines 
lose  water  and  are  converted  into  anhydrides  known  as  epi-chlor 
hydrines.  The  reactions  take  place  most  readily  with  the  alpha-chlor 


MIXED   POLY-SUBSTITUTION   PRODUCTS  225 

hydrines,  as  in  the  first  reaction,  but  also  with  the  fo/a-compounds 
as  in  the  second  reaction. 


CH2—  Cl 

CH2—  Cl 

CH2—  OH 

1" 

CH2X 

CH-OH     1^!? 

1 

CH            and 

1      > 

CH—  Cl     _!? 

|         \ 
CH—  cf>O 

CH2—  OH 

CH/ 

CH2—  OH 

CH/ 

a-Chlor  hydrine 

Epi-a-chlor 
hydrine 

0-Chlor  hydrine 

Epi-/3  -chlor 
hydrine 

II.  AMINO  ALCOHOLS 

From  the  chlor  hydrines,  by  means  of  ammonia,  we  can  pass  to  the 
corresponding  amino-alcohols, 

CH2—  Cl  CH2—  NH2 

+  NH3  ->  |  +HC1 

CH2—  OH  CH2—  OH 

Glycol  chlor  hydrine  i-Amino  a-hy- 

-droxy  ethane 

The  most  important  reaction,  however,  for  the  formation  of  the  amino 
alcohols,  is  that  of  ammonia  and  aldehydes,  (p.  116). 

H  H 

R—  C  =  O      +      H—  NH2  -  >  R—  C—  OH 

Aldehyde 

NH2 

Aldehyde  ammonia 

In  this  case  the  amino  group  is  united  to  the  same  carbon  as  the 
hydroxyl. 

III.  CYANOGEN  ALCOHOLS 

Cyanogen-hydroxyl  Compounds.  —  The  cyanogen-alcohols  are  very 
similar  to  the  amino-alcohols  in  their  methods  of  formation.  They 
may  be  formed  from  the  chlor-hydrines  by  the  action  of  potassium 
cyanide,  as  follows: 

CH2(C1)—  CH2—  OH  +  K—  CN        -  >        CH2(CN)—  CH2—  OH 

Chlor  hydrine  Cyanogen  alcohol 

(Nitrite  of  a  hydroxy  acid) 

In  this  case  the  cyanogen  and  hydroxyl  groups  are  linked  to  different 
carbons.     They  may  also  be  formed  from  the  aldehydes  by  the  addition 

15 


226  ORGANIC  CHEMISTRY 

of  hydrogen  cyanide,  in  which  case  the  cyanogen  group  is  linked  to  the 
same  carbon  as  the  hydroxyl, 

H  H  Aldehyde 

|  hydrogen 

Aldehyde  R-C  =  0    +  H-CN  — >        R-C -OH  cyanide 

Cyanogen 
CN          alcohol 
The  cyanogen  alcohols  are  nitriles  of  hydroxy  acids. 

C.  SUBSTITUTED  ALDEHYDES  AND  KETONES 

I.  HALOGEN  ALDEHYDES 
Tri-chlor  Aldehyde    CC13— CHO     Chloral 

When  aldehydes  are  directly  halogenated  the  halogen  enters  a 
carbon  group  other  than  the  one  containing  the  aldehyde  group.  In 
the  case  of  acet-aldehyde  chlorine  may  be  substituted  for  all  three  of 
the  hydrogens  in  the  methyl  radical  and  we  obtain,  tri-chlor  acet- 
aldehyde  : 

CH3  -  CHO  +  3Ci;       >       CC13  -  CHO   +    3HC1 

Aldehyde  Tri-chlor  aldehyde 

Chloral 

It  will  be  recalled  that  this  compound  is  the  intermediate  product 
in  the  formation  of  chloroform  from  alcohol.  The  alcohol  is  first 
oxidized  to  aldehyde  by  means  of  chlorine,  (p.  115),  the  substitution  of 
chlorine  in  the  aldehyde  then  taking  place  as  above. 

It  is  possible  that  this  oxidation  takes  place  by  the  loss  of  hydrogen 
through  the  direct  action  of  chlorine  without  the  action  of  oxygen  (p. 
222). 

H  H  H 

I  I  -HC1  I 

CH3— C— OH  +  C1     >      CH3— C— 0(H)      _:;      CH3— C  =  O 

Aldehyde 

H  (Cl) 

Alcohol 

In  the  preparation  of  chloroform  the  tri-chlor  acet-aldehyde  then  reacts 
with  an  alkali  present  yielding  chloroform  and  the  .alkali-metal  salt  of 
formic  acid,  as  follows : 

CC1"3—  (CHO  +  NaO)— H        >        CHC13    +    H— COONa 

Tri-chlor  acet-  Chloroform  Sodium  formate 

aldehyde 


MIXED   POLY-SUBSTITUTION   PRODUCTS  227 

Chloral.  —  Chloral,  or  tri-chlor  acet-aldehyde,  was  first  prepared  by 
Liebig  in  1832  by  the  chlorination  of  alcohol  as  above.  It  may  also  be 
obtained  by  the  direct  action  of  chlorine  upon  acet-aldehyde.  It  is  an 
oily  liquid  with  a  sweet  suffocating  odor.  It  boils  at  97.7°.  It  does 
not  mix  with  water  but  on  boiling  with  water  it  forms  a  hydrated  com- 
pound which  crystallizes  in  large  clear  crystals,  readily  soluble  in  water. 
This  is  known  as  chloral  hydrate.  The  structure  of  chloral  hydrate  is 
probably  that  of  an  addition  product,  viz.,  a  chlorinated  di-hydroxy 
alcohol.  In  this  compound  we  have  an  exception  to  the  general  rule 
that  two  hydroxyl  groups  can  not  be  linked  to  the  same  carbon  atom. 

H  H 

!  I 

CC13—  C  =  O  +  H—  OH        -  >        CC13—  C—  OH 

Chloral 

OH 

Chloral  hydrate 

This  constitution  of  the  hydrate  is  indicated  by  the  fact  that  it  does  not 
give  the  aldehyde  reaction  with  fuchsine  as  does  both  acet-aldehyde  and 
chloral.  Also  by  the  fact  that  the  ethyl  ester  of  such  a  di-hydroxy 
alcohol  is  known  and  is  formed  from  chloral  by  reaction  with  alcohol. 

H  H 

|  | 

CC13—  C  =  O  +  C2H5—  OH        -  >        CC13—  C—  OH 

Chloral 

OC2H5 

Chloral  alcoholate 

Similar  addition  products  of  chloral  and  ammonia  and  of  chloral  and 
hydroxyl  amine  are  also  known. 

H  H  H 


CC13—  C—  OH       «=  CC13—  C  =  O  >3       CC13-C-OH 

I  Chloral 

NH-OH  NH2 

Chloral  hydroxyl  amine  Chloral  ammonia 

The  formation  of  addition  products  with  chloral  is  much  easier 
than  with  acet-aldehyde  itself,  due  to  the  influence  of  the  three  negative 
chlorine  atoms  in  the  alkyl  radical.  Chloral  undergoes  polymerization, 
as  does  acet-aldehyde,  the  product  being  meta-chloral  (CC13CHO)3. 


228  ORGANIC  CHEMISTRY 

It  reduces  ammoniacal  silver  nitrate  solution.  It  is  oxidizable  to 
tri-chlor  acetic  acid  and,  by  the  action  of  zinc  and  hydrochloric  acid,  is 
reduced  to  acet-aldehyde.  Chloral  is  a  most  important  soporific  and 
is  used  in  certain  cases  for  anesthetic  purposes.  In  this  latter  use  it  is 
always  the  readily  soluble  form  of  chloral  hydrate  which  is  employed. 
Its  anesthetic  action  was,  at  first,  attributed  to  the  probable  formation 
of  chloroform  but  this  is  now  doubted. 

II.  HALOGEN  KETONES 

Halogen-ketones  are  similarly  obtained  by  direct  halogenation  of 
ketones.  In  the  case  of  acetone,  or  propanone,  all  six  possible  chlor 
acetones  are  known,  and  are  obtained  either  by  direct  chlorination,  or 
by  other  reactions,  which  we  need  not  discuss  here. 

CCk 

C  =  O  +  6C12        -  >  )C  =  O  +  6HC1 

CC\/ 

Acetone  Hexa-chlor  acetone 

III.  HYDROXY  ALDEHYDES  AND  HYDROXY  KETONES 

When  poly-hydroxy  alcohols  are  oxidized  the  first  product  is  a 
compound  in  which  one  of  the  alcohol  groups  has  been  oxidized  either 
to  aldehyde  or  to  ketone  depending  on  whether  the  alcohol  group  is 
primary  or  secondary. 

Aldehyde  Alcohols.  —  From  the  simplest  poly-hydroxy  alcohol 
glycol  or  ethandiol,  the  only  product  of  this  kind  that  is  possible  is  an 
aldehyde-alcohol  known  as  glycolic  aldehyde. 


CH2OH—  CH2OH  >       CH2OH—  CHO 

Glycol  Glycolic  aldehyde 

Ketone  Alcohols.  —  From  the  higher  poly-hydroxy  alcohols  however, 
which  contain  both  primary  and  secondary  alcohol  groups  we  obtain 
both  aldehyde  alcohols  and  ketone  alcohols.  Glycerol  or  propantriol 
thus  yields  the  following: 


CH2OH—  CHOH—  CH2OH  >     CH2OH—  CHOH—  CHO 

Glycerol  Glyceric  aldehyde 


CH2OH—  CHOH—  CH2OH        _.>        CH2OH—  CO—  CH2OH 

Di-hydroxy  acetone 


MIXED   POLY-SUBSTITUTION   PRODUCTS  22Q 

Both  the  hydroxy  aldehydes  or  aldehyde  alcohols  and  the  hydroxy 
ketones  or  ketone  alcohols  undergo  the  characteristic  aldehyde  and 
ketone  reactions  due  to  the  carbonyl  group.  They  react  with  hydrogen 
cyanide,  phenyl  hydrazine  and  hydroxyl  amine.  These  reactions  have 
been  discussed  in  connection  with  the  aldehydes  (pp.  116,  224)  and 
will  be  considered  again  when  we  study  the  carbohydrates.  The 
carbohydrates  in  fact  belong  here  with  these  hydroxy  aldehyde  and 
hydroxy  ketone  compounds  but  on  account  of  other  relations  they 
are  better  considered  at  a  later  time. 
Glycolic  Aldehyde  CH2OH—  CHO.  Glyceric  Aldehyde  CH2OH—  CHOH—  CHO 

The  simplest  member  of  the  group,  as  given  above,  is  known  as 
glycolic  aldehyde  and  is  obtained  only  in  the  form  of  its  water  solution. 
It  derives  its  name  as  do  other  aldehydes  from  the  fact  that  it  yields 
glycolic  acid  on  oxidation.  Glyceric  aldehyde  and  di  -hydroxy 
acetone  the  oxidation  products  of  glycerol  (p.  200)  are  very  important 
as  they  together  constitute  the  simplest  sugar  that  is  known  and  the  first 
one  synthesized  (p.  320). 

Aldol  CH3—  CH(OH)—  CH2—  CHO.     0-Hydroxy  Butyric  Aldehyde 

This  compound  is  an  important  and  interesting  member  of  the 
group.  It  is  made  by  the  condensation  of  two  molecules  of  acet-alde- 
hyde  (p.  116).  The  reaction  is,  therefore,  known  as  the  aldol  conden- 
sation and-in  its  general  form  is  characteristic  of  aldehydes  taking  place 
also  with  the  hydroxy  aldehydes,  e.g.,  with  glycolic  aldehyde, 
H 

(Aldol  con- 
CH3—  C  =  O  +  H—  CH2—  CHO 

Acet-aldehyde  dCHSCUion) 

H 
CH3—  C(OH)—  CH(H)—  CHO     1?!?    CH3—CH  =  CH—  CHO 


Aldol  is  oxidizable  to  hydroxy  butyric  acid  and,  being  a  beta-hydroxy 
compound,  loses  water  yielding  an  unsaturated  aldehyde,  crotonic 
aldehyde  (p.  169),  as  in  the  second  part  of  the  reaction. 

D.  SUBSTITUTED  ACIDS 

The  mixed  compounds  which  we  have  been  considering  may  be 
regarded  as  mono-substitution  products  of  that  class  of  compounds 


230  ORGANIC  CHEMISTRY 

characterized  by  the  other  group  present.  The  chlor-hydrines,  e.g., 
may  be  regarded  as  chlorine  substitution  products  of  alcohols  and 
similarly  chloral,  CC13  —  CHO,  is  a  substituted  aldehyde.  We  should 
expect,  therefore,  to  have  acids  in  which  substitution  of  other  groups  or 
elements  occurs  giving  the  general  group  of  compounds  which  we  would 
designate  as  substituted  acids.  These  are  the  compounds  which  we 
have  now  to  consider  and  we  shall  naturally  find  different  sub-classes 
corresponding  to  the  different  substitution  products  of  the  hydro- 
carbons themselves.  We  shall  have  to  consider,  then,  as  mixed  acid  com- 
pounds (a)  halogen  acids,  (b)  amino  acids,  (c)  cyanogen  acids,  and  (d) 
hydroxy  acids,  in  all  of  which  the  other  substituting  group  is  different 
in  character  from  the  carboxyl  group.  The  amino-acids  will  be  dis- 
cussed by  themselves,  later,  as  they  are  closely  related  to  the  proteins, 
which  we  do  not  wish  to  consider  at  this  time.  Similarly  the  cyanogen 
acids  will  not  be  taken  up  now,  for  they  are  plainly  nitriles  of  the  di- 
carboxy  acids  and  on  that  account  will  be  better  considered  directly 
in  connection  with  these  latter  compounds.  There  remains,  then,  for 
discussion  at  this  time  the  two  classes  of  halogen  acids  and  hydroxy 
acids. 

I.  HALOGEN  ACIDS 

The  halogen  acids,  of  course,  bear  the  same  relation  to  the  halogen 
aldehydes  and  the  halogen  alcohols  (halogen  hydrines)  that  unsubsti- 
tuted  acids  do  to  the  unsubstituted  aldehydes  and  alcohols.  That  is, 
they  are  the  direct  oxidation  products. 


CH3—  CH2OH    __>    CH3—  CHO  CH3—  COOH 

Alcohol  Aldehyde  Acid 


CH2C1—  CH2OH  ,     CH2C1—  CHO  CH2C1—  COOH 

Halogen  alcohol  Halogen  aldehyde  Halogen  acid 

This  reaction  of  oxidation  often  takes  place,  as  has  been  referred  to  in 
the  case  of  tri-chlor  aldehyde,  or  chloral,  which  yields  tri-chlor  acetic 
acid  on  oxidation.  But  this  is  not  the  ordinary  method  of  preparation 
of  the  halogen  acids.  The  common  method  of  preparing  these  com- 
pounds is  by  the  direct  halogenation  of  the  acids  themselves. 

Halogenation  of  Acids.  —  Several  facts  are  of  especial  importance 
in  connection  with  the  halogenation  of  the  saturated  acids.  In  most 
cases  the  introduction  of  the  halogen  element  into  the  acid  takes  place 
with  comparative  ease.  It  may  be  by  the  direct  action  of  the  halogen, 


HALOGEN   MONOBASIC   ACIDS  231 

(chlorine,  for  example)  at  ordinary  raised  temperatures,  or  by  the  ac- 
tion of  the  halogen  in  the  presence  of  a  carrier.  It  is  also  interesting 
that  the  higher  the  molecular  weight  of  the  acid,  i.e.,  the  higher  the 
acid  stands  in  the  homologous  series,  the  more  easily  does  substitution 
occur.  For  example,  to  form  brom  acetic  .acid  it  is  necessary  to  heat 
acetic  acid  with  bromine  in  a  sealed  tube  for  100  hours.  Propionic 
acid,  however,  is  brominated  by  heating  for  40  hours,  while  butyric  acid 
requires  similar  heating  for  only  7  hours,  in  order  to  accomplish  bromina- 
tion.  Such  substitution  of  halogens  takes  place  with  the  acids  them- 
selves, but  still  more  easily  with  the  acid  anhydrides  or  the  acid  chlorides. 
The  method  of  brominating  most  commonly  used  is  to  treat  the  acid 
with  red  phosphorus  and  then  to  add  bromine.  The  first  reaction  is  to 
form  the  acid  bromide,  (e.g.) 


>  3CH3—  CO—  Br-f-  P(OH)3 

Acetic  acid  Acetyl  bromide 

The  bromine  then  acts  directly  upon  the  acid  bromide  forming 
brom  acetyl  bromide,  which,  by  the  action  of  water,  is  hydrolyzed  yield- 
ing brom  acetic  acid,  as  follows: 

CH3—  CO—  Br  +  Br2  -  >  HBr  +  CH2Br—  CO—  Br  +  H2O    -  > 

Acetyl  bromide  Brom  acetyl  bromide 

CH2Br—  COOH  +  HBr 

Brom  acetic  acid 

Nomenclature  of  Substituted  Acids.  —  In  the  case  of  acids  which  con- 
tain more  than  two  carbon  groups  the  substitution  may  take  place  in 
any  of  the  carbon  groups  other  than  the  carboxyl.  To  distinguish  these 
isomeric  acids  by  name  the  position  of  the  substitution  is  indicated  by 
means  of  the  Greek  letters,  alpha  (a),  beta  (0),  gamma  (7),  delta  (6), 
epsilon  (e),  etc.,  beginning  with  the  carbon  adjoining  the  carboxyl 
group.  Normal  caproic  acid  would  thus  have  the  different  carbons 
designated  as  follows,  CH3—  CH2—  CH2—  CH2—  CH2—  COOH. 
€  8  7  |8  a 

By  the  method  of  halogenation  just  described  the  halogen  always 
enters  the  alpha  position.  In  the  case  of  isomeric  branched  chain  com- 
pounds, in  which  the  alpha  carbon  has  no  remaining  hydrogen  atom 
united  to  it,  direct  substitution  does  not  take  place.  To  form  halogen 
acids  from  acids  of  this  character  other  methods  of  preparation  must 
be  employed. 

In  case  direct  halogenation  is  continued  for  some  time  beyond 


232  ORGANIC  CHEMISTRY 

that  required  for  substitution  of  one  halogen  atom,  then  more  than  one 
halogen  is  substituted  up  to  the  limit  of  the  alpha  carbon.  Thus  acetic 
acid  yields,  finally,  tri-halogen  acetic  acid, 

CH3— COOH >     CH2C1— COOH    >     CHC12— COOH    > 

Acetic  acid  Mono-chlor  acetic  acid  Di-chlor  acetic  acid 

CC13— COOH 

Tri-chlor 
acetic  acid 

Propionic  acid  yields  first  the  mono-  and  then  the  di-halogen  propionic 
acid, 

CH3— CH2— COOH-   CH3— CHBr— COOH     CH3— CBr2— COOH 

Propionic  acid  a-Mono-brom  a-a-Di-brom  propionic  acid 

propionic  acid 

For  the  preparation  of  halogen  acids  in  which  the  substitution  is  in  the 
beta  or  gamma  position  the  reaction  of  the  unsaturated  acids  of  the  ethyl- 
ene  series  is  usually  employed.  As  ethylene  by  the  addition  of  hydro- 
bromic  acid  yields*  brom  ethane,  so  in  like  manner,  unsaturated  acids 
of  the  ethylene  series  take  up  halogen  acids  and  pass  to  the  mono-halo- 
genated  saturated  acid, 

CH2  =  CH2  +  HBr       — »     CH3— CH2Br 

Ethene  Mono-brom  ethane 

CH2  =  CH— COOH  +  HC1       —>    CH2C1— CH2— COOH 

Propenoic  acid  /3-Chlor  propanoic  acid 

CH3— CH  =  CH— CH2— COOH  +  HBr    > 

Az-Pentenoic  acid 

CH3— CHBr— CH2—CH2— COOH 

7-Brom  pentanoic  acid 

By  means  of  the  similar  reaction  with  halogens  alone  the  unsatu- 
rated acids  yield  di-halogen  saturated  acids, 

CH3— CH  =  CH— COOH  +  Br2  >  CH3— CHBr— CHBr— COOH 

A2-Butenoic  acid  a-j8-Di-brom  butanoic  acid 

General  Properties. — The  halogen  acids  are  characteristically 
acid  compounds  undergoing  all  acid  reactions  and  yielding  derivatives 
corresponding  to  the  acid  from  which  they  are  derived.  They  form, 
therefore,  anhydrides,  salts,  esters,  acid  chlorides,  and  acid  amides. 
In  fact,  the  acid  character  of  the  halogen  acids  is  more  pronounced 
than  that  of  the  original  unsubstituted  acids  themselves.  This  is  due 
to  the  presence  of  the  additional  negative  group,  i.e.,  the  halogen  con- 
taining group.  Also,  the  more  halogen  atoms  substituted  the  stronger 
is  the  acid  property.  This  increasing  acid  character  may  be  illustrated 


HALOGEN   MONOBASIC   ACIDS  233 

by  giving  the  electric  conductivity,  or  dissociation  constant,   of  the 
halogen  acetic  acids. 

Acid  Dissociation  constant 
CH3— COOH      Acetic  acid,  0.0018 

CH2C1 — COOH  Mono-chlor  acetic  acid,  0.1550 

CHC12— COOH  Di-chlor  acetic  acid,  5.1400 

CC13— COOH     Tri-chlor  acetic  acid,  1 2 1 .0000 

Reactions.— The  halogen  acids  react  also  like  alkyl  halides.  With 
ammonia  they  yield  amino  acids,  and  with  potassium  cyanide  the 
products  are  cyanogen  acids,  or  nitriles. 

CH3— Cl  +  NH3        >        CH3— NH2 

Methyl  Methyl  amine 

chloride 

CH2C1— COOK  +  NH3         >        CH2(NH2)— COOK 

Chlor  acetic  acid  Amino  acetic  acid 

(salt)  (salt) 

CH3— Cl  +  KCN >        CH3— CN 

Methyl  Methyl 

chloride  cyanide 

CH2C1— COOK  +  KCN  — >         CH2(CN)— COOK 

Chlor  acetic  acid  Cyanogen  acetic  acid 

(salt)  (salt) 

Alpha-,  Beta-,  and  Gamma-Acids. — The  replacement  of  the  halo- 
gen by  hydroxyl  takes  place  readily  in  the  case  of  the  a/^a-halogen 
acids,  by  simply  heating  with  water  or  with  alkalies, 

CH2C1— COOH  +  H— OH    >    CH2(OH)— COOH 

a-Halogen  acid  or-Hydroxy  acid 

Unsaturated  Hydrocarbons. — In  the  case  of  beta-halogen  acids 
the  reaction  takes  place  differently.     When  these  are  heated  with  water 
and  alkali  they  lose  carbon  dioxide  and  the  halogen-hydrogen  acid, 
an  unsaturated  hydrocarbon  resulting. 
CH3 

-HBr 
CH3CH(Br)— C(H)— COOH+NaOH CH3— CH  =  CH— CH3 

/3-Brom  z-methyl  butanoic  acid  —  CO2  Butene 

The  same  is  true  of  the  alpha-beta-di-halogen  acids,  which,  by  the 
loss  of  halogen-hydrogen  acid,  yield  halogen  unsaturated  compounds. 

-HBr 
CH3— CH(Br)— C(H)Br— (COO)H-f-KOH    -    —    CH3— CH  =  CHBr 

a-B-Di-brom  butanoic  acid  •     — CO2  i-Brom  propene 


234  ORGANIC  CHEMISTRY 

Inner  Anhydrides.  —  The  gamma-halogen  acids  undergo  a  yet  differ- 
ent decomposition  by  the  action  of  alkalies,  as  follows: 


CH3—  CH(Br)—  CH2—  CH2—  COO(H)  +  KOH 

7-Brom  pentanoic  acid         CH3—  CH—  CH2—  GH2—  CO  +  KBr 

-o- 

An  inner  anhydride 

In  this  case  we  have  formed  an  inner  anhydride  which  will  be  ex- 
plained presently,  when  we  consider  the  hydroxy  acids.  These  differ- 
ences in  the  reaction  of  alpha-,  beta-  and  gamma-halogen  acids  are 
characteristic  of  alpha-,  beta-.,  and  gamma-substituted  acids  in  general 
and  will  be  more  clearly  shown  when  we  consider  them  in  connection 
with  the  hydroxy  acids  (p.  241). 

Chlor-formic  Acid 

The  simplest  possible  halogen  acid  is  the  one  derived  from  formic 
acid  by  substituting  a  halogen  atom  for  the  non-carboxyl  hydrogen, 

H—  COOH        -  >        Cl—  COOH         Cl—  COOC2H5 

Formic  acid  Chlor-formic  acid  Chlor  formic  acid 

(Ethyl  ester) 

This  acid  is  not  known  in  the  free  state  but  as  the  ethyl  ester.  As  will 
be  shown  later  chlor  formic  acid  may  also  be  considered  as  a  derivative 
of  carbonic  acid  and  as  this  is  its  most  important  relation  a  fuller 
discussion  will  be  deferred  until  carbonic  acid  is  discussed  (p.  428). 

Chlor-acetic  Acids 

In  the  case  of  acetic  acid  three  halogen  substitution  products  are 
possible.  Illustrating  with  the  chlorine  acids  the  formulas  are: 

Acetic  acid,  CH3—  COOH  CHC12—  COOH  Di-chlor 

acetic  acid. 

Mono-chlor      CH2C1—  COOH  CC13—  COOH  Tri-chlor 

acetic  acid,  acetic  acid. 

Mono-chlor  acetic  acid  is  a  solid  which  forms  colorless  crystals  melting 
at  63°  and  boiling  at  i85°-i87°.  Its  vapors  are  very  irritating  causing 
the  flow  of  tears  and  blistering  the  skin.  Di-chlor  acetic  acid  is  a 
liquid  at  ordinary  temperatures  with  a  boiling  point  of  189°-!  91°. 
The  common  method  of  preparing  this  acid  is  not  by  one  of  the  reactions 
already  given  but  by  the  action  of  potassium  cyanide  upon  tri-chlor 


HALOGEN   MONOBASIC   ACIDS 


235 


aldehyde  (chloral).  The  reaction  is  somewhat  complicated  and  is 
probably  due  to  the  real  action  of  water.  It  may  be  represented  as 
follows  : 

H  OH 

I  0(H                                      j 

(C1)CC12—  C  =  0  +      1           —  >        H—  CC12—  C  =  O     +     HC1 

Tri-chlor  aldehyde  /N                                            Di-chlor  acetic  acid 


Tri-chlor  acetic  acid  is  a  solid  forming  deliquescent  crystals  which 
melt  at  52°  and  boil  at  195°.  It  is  strongly  caustic  and  is  used  in  medi- 
cine on  account  of  this  property.  It  is  readily  decomposed  by  boiling 
its  solution,  yielding  chloroform  and  carbon  dioxide, 

CC13—  (COO)H  -  >  CHC13  +  C02 

Tri-chlor  acetic  acid  Chloroform 

This  reaction  is  analogous  to  the  decomposition  of  saturated  acids 
which,  by  the  loss  of  carbon  dioxide,  yield  the  corresponding  hydro- 
carbon. The  halogen  acid,  however,  undergoes  the  decomposition 
much  more  easily  than  the  unsubstituted  acid.  Though  so  closely 
related  to  both  chloroform  and  chloral,  tri-chlor  acetic  acid  does  not 
possess  either  soporific  or  anaesthetic  properties.  If  the  soporific 
action  of  chloral  is  due  to  the  formation  of  chloroform  in  the  body,  it 
would  seem  that  tri-chlor  acetic  acid  should  also  act  as  a  soporific 
as  it  decomposes  and  yields  chloroform  as  easily  as  does  chloral.  This 
is  one  reason  for  claiming  that  the  soporific  action  of  chloral  is  not  con- 
nected with  its  decomposition  into  chloroform.  The  three  chlor  acetic 
acids  are  of  especial  importance  historically  in  connection  with  the 
development  of  ideas  in  regard  to  substitution  as  advanced  by  Dumas 
(p.  9).  The  fact  that  acetic  acid  in  which  hydrogen  (electro  positive) 
was  substituted  by  chlorine  (electro  negative),  yielding  compounds 
possessing  all  the  properties  of  the  original  acetic  acid,  being  even  more 
strongly  acid  than  the  acetic  acid  itself,  was  in  accordance  with 
ideas  of  Dumas,  that  one  element  could  be  substituted  for  another 
and  act  like  the  one  substituted.  It  was,  however,  in  direct  opposition 
to  the  electro-chemical  theory  as  advanced  and  upheld  by  Berzelius,  for, 
by  this  theory,  an  electro  positive  element  could  not  be  replaced  -by  an 
electro  negative  one.  The  other  important  halogen  acids  need  not  be 
considered  in  detail.  When  they  are  involved  in  future  discussions 
they  will  be  mentioned.  Neither  need  we  consider,  in  detail,  the  halo- 
gen unsaturated  acids.  Enough  has  been  said  in  regard  to  the  general 


236  ORGANIC  CHEMISTRY 

properties  of  these  substituted  acids,  their  formation  and  reactions,  to 
lead  us  to  understand  any  unsaturated  acid  of  like  character.  The 
substituted  unsaturated  acids  bear  exactly  the  same  relation  to  sub- 
stituted saturated  acids  that  the  acids  themselves  bear  to  each  other 
and  which  has  been  fully  discussed  in  the  chapter  on  unsaturated  acids. 

II.  HYDROXY  ACIDS 

The  hydroxy  acids  are  the  most  important  of  all  the  classes  of 
substituted  acids.  Many  of  them  occur  as  constituents  of  plants  or 
animals  and  they  are  closely  related  to  other  important  natural  prod- 
ucts such  as  the  sugars.  They  result  from  the  substitution  of  the 
hydroxyl  group,  ( — OH),  for  hydrogen  of  the  alkyl  radical  in  acids. 
Being  mixed  alcohol  and  acid  compounds,  they  possess  the  properties 
of  both  classes  of  compounds  represented  and  these  properties  are  like 
as  well  as  different. 

As  we  have  not  yet  studied  the  poly-carboxy  compounds  our  present 
discussion  will  include  only  the  mono-hydroxy  and  the  poly-hydroxy 
substitution  products  of  the  mono-carboxy  acids  (mono-basic  acids). 
The  hydroxyl  derivatives  of  the  poly-carboxy  acids  will  be  considered 
in  connection  with  these  acids  when  we  come  to  them. 

Syntheses. — The  general  methods  for  the  synthesis  of  hydroxy  acids 
are  numerous,  because  the  reactions  that  have  been  used  for  the  prepa- 
ration of  both  alcohols  and  acids  are  applicable.  We  have  two  general 
types  of  synthetic  reactions. 

I.  The  introduction  of  the  hydroxyl  group,  or  groups,  into  mono- 
carboxy  acids.    These  reactions  will  be  analogous  to  those  used  for  the 
synthesis  of  alcohols. 

II.  The  introduction  of  the  carboxyl  group,  or  of  some  group  yielding 
carboxyl,   e.g.,   the  cyanogen  group,   (  — CN),  into  mono-hydroxy  or 
poly-hydroxy  alcohols.    These  will  be  analogous  to  the  reactions  used 
for  the  synthesis  of  acids. 

Alcohol-like  Syntheses.  From  Halogen  Acids. — The  simplest 
method  of  synthesizing  hydroxy  acids,  similar  to  methods  for  the 
synthesis  of  alcohols,  is  from  the  corresponding  halogen  compounds. 

i.' Halogen  acids  by  reaction  with  water,  H— OH,  potassium,  or 
sodium  hydroxide,  K— OH,  Na— OH,  or  silver  hydroxide,  Ag  — OH, 
yield  hydroxy  acids  by  replacing  the  halogen  with  hydroxyl. 

CH2C1-COOH  +  H-OH    >    CH2(OH)-COOH  +  HC1 

Chlor  acetic  acid  Hydroxy  acetic  acid 


HYDROXY  MONOBASIC  ACIDS  237 

From  Amino  Acids. — 2.  Amino  acids,  by  diazotization  and  sub- 
sequent decomposition  of  the  resulting  diazo  compound  with  water, 
yield  hydroxy  acids  by  the  replacement  of  the  amino  group  with 
hydroxyl.  These  reactions  will  be  considered  when  the  amino  acids 
are  studied. 

Acid -like  Syntheses.  From  Cyan  Hydrines. — 3.  Cyan  hydrines, 
alcohol-cyanogen  compounds,  when  hydrolized  yield  hydroxy  acids  by 
the  conversion  of  the  cyanogen  group  into  the  car  boxy  I  group.  As 
stated  under  the  cyan  hydrines  (p.  225),  and  also  under  aldehydes 
(p.  1 1 6),  these  alcohol-cyanogen  compounds  are  formed  from 
aldehydes  or  ketones  by  the  addition  of  hydrogen  cyanide.  The 
double  reaction  will  be,  then,  as  follows: 

H  H 

I      .                                                    I 
CH3-CH2-C  =  O  +  H-CN >  CH3-CH2-C-CN+2H2O > 

Propionic  aldehyde 
Propan-al 

OH 

Cyan  hydrine 
Acid  nitrile 

H 

I 
CH3-CH2-C-COOH 

I 
OH 

Ta-Hydroxy  butyric  acid 
2-Hydroxy  butanoic  acid 

OH 
CH3-C  =  O  +  H-CN  >  CH3-C-CN+2H2O   — > 


CH3  CH3 

Acetone  Cyan  hydrine 

Propanone  Acid  nitrile 


OH 

CH3-C-COOH 

I 
CH3 

a-Hydroxy  iso-butyric  acid 
2-Hydroxy  2 -methyl 
propanoic  acid      __    . 


238  ORGANIC  CHEMISTRY 

From  aldehydes,  we  always  obtain  an  alpha-hydroxy  acid  in  which  the 
hydroxyl  group  is  linked  to  the  carbon  atom  which  is  itself  directly 
linked  to  carboxyl.  Also  the  resulting  hydroxy  acid  will  always  con- 
tain one  more  carbon  than  the  aldehyde  with  which  we  start.  Thus,  by 
starting  with  any  saturated  alcohol  or  acid  and  obtaining  the  aldehyde, 
we  may  pass  to  the  hydroxy  acid  next  higher  in  the  series.  Acetic 
aldehyde  yields  a-hydroxy  propionic  acid.  From  ketones  we  also  always 
obtain  an  alpha-hydroxy  acid  and  likewise  increase  the  number  of 
carbon  atoms  by  one.  The  alpha-hydroxy  acid  obtained,  however,  will 
be  isomeric  with  the  one  obtained  from  the  aldehyde  of  equal  carbon 
content.  This  will  be  seen  from  the  above  reactions. 

The  hydroxy  acids  obtained  from  aldehydes  will  contain  the  group, 
.  —  CH(OH)  — COOH,  and  are  thus  secondary  alcohols  while  those  ob- 
tained from  ketones  will  contain  the  group,  =  C(OH)  — COOH,  and 
are  tertiary  alcohols.  These  reactions  are  of  especial  importance  in 
connection  with  the  poly-hydroxy  aldehydes  and  ketones,  which,  as 
we  shall  find,  are  the  sugars.  The  cyan  hydrines,  or  hydroxy  acid 
nitriles,  which  are  the  intermediate  products  in  these  reactions,  are 
not  isolated  as  such,  the  reaction  being  completed  without  interruption. 

From  Poly-hydroxy  Alcohols. — 4.  Poly-hydroxy  alcohols  by  oxida- 
tion, yield  poly-hydroxy  acids.  In  this  case,  of  course,  only  primary 
alcohol  groups,  (  — CH2OH),  can  yield  carboxyl  and  these  groups  must, 
necessarily,  be  at  the  end  of  the  carbon  chain.  The  oxidation  must  be 
mild  so  that  only  one  alcoholic  group  shall  be  affected. 

CH2(OH)  -  CH(OH)  -  CH2(OH)  +  O    > 

Glycerol 

CH2(OH)-CH(OH)-CHO  +  O  >   CH2(OH)-CH(OH)-COOH 

Glyceric  aldehyde  Glyceric  acid 

As  the  poly-hydroxy  aldehydes,  or  sugars,  are  the  intermediate  products 
in  this  reaction  it  is  practically  the  same  synthesis  if  we  start  with  the 
sugars  and  oxidize  them  to  the  corresponding  poly-hydroxy  acids. 

From  Unsubstituled  Acids. — 5.  It  will  be  recalled  that  hydrocar- 
bons can  not  be  oxidized  directly  to  the  formation  of  alcohols.  The 
reaction  which  we  represent  as  such  (p.  114),  is  purely  hypothetical 
and  is  used  to  show  the  steps  in  the  complete  oxidation  of  a  hydrocarbon 
in  the  formation  of  the  successive  oxidation  products,  viz.,  alcohols, 
aldehydes  and  acids.  When,  however,  we  have  an  acid  in  which  there 


HYDROXY   MONOBASIC    ACIDS  239 

is  a  tertiary  carbon  atom,  e.g.,  (R)2  =  CH  —  COOH,  the  tertiary  carbon  on 
oxidation  has  the  hydrogen  atom  oxidized  to  hydroxyl,  as  follows: 

CH3-CH-COOH  +  O2    -  >     CH3-C(OH)-COOH 

!  I 

CH3  CH3 

Iso-butyric  acid  a-Hydroxy  iso-butyric  acid 

2-Methyl  propanoic  acid  2-Hydroxy  a-methyl  propanoic  acid. 

Reactions  and  Products.  Ethers.  —  Being  both  alcohols  and  acids 
the  hydroxy  acids  undergo  reactions  and  yield  products  characteristic 
of  both  classes  of  compounds,  (i)  As  acids  they  form  metallic  salts, 
acid  chlorides  and  acid  amides,  which  are  exactly  analogous  to  those 
formed  from  the  acetic  acid  series  both  as  to  methods  of  formation  and 
properties.  These  need  not  be  discussed  further.  (2)  They  form 
ethers  with  other  alcohols,  in  this  case  reacting  as  an  alcohol.  These 
new  compounds  will  be  mixed  ether  and  acid  compounds. 


CH3—  (OH  +  H)O—  CH2—  COOH  !        CH3—  O—  CH2—  COOH 

Methyl  alcohol  Hydroxy  acetic  Methyl  ether  of  hydroxy 

acid  acetic  acid 

[(Ether  acid) 

These  ethers  are  usually  formed  by  the  reaction  of  an  alcoholate  with 
an  ester  of  a  halogen  acid,  the  reaction  being  analogous  to  the 
Williamson  synthesis  of  ether. 

C2H5O—  (Na  +  Cl)—  CH2—  COOR        —  -> 

Sodium  ethylate  Ester  of 

chlor  acetic  acid 

>     C2H5—  O—  CH2—  COOR  +  NaCl 

Ethyl  ether  of 
hydroxy  acetic  acid  ester 

Not  only,  however,  do  the  hydroxy  acids  form  ethers  with  other  alco- 
hols but  they  will  react  in  the  same  way  with  themselves,  the  alcohol 
group  of  one  molecule  forming  an  ether  with  the  alcohol  group  of  a 
second  molecule. 


HOOC—  CH2—  (OH  +  H)O—  CH2—  COOH     1! 

Hydroxy  acetic  acid 

HOOC—  CH2—  O—  CH2—  COOH 

Di-(hydroxy  acetic  acid)  ether 
Di-glycolic  acid 


240  ORGANIC  CHEMISTRY 

The  ether  which  is  obtained  in  small  yields  by  heating  the  hydroxy 
acid  is  more  easily  prepared  by  the  reaction  between  two  molecules 
of  chlor  acetic  acid  and  potassium  hydroxide.  As  this  reaction  prob- 
ably takes  place  in  two  steps,  the  hydroxy  acetic  acid  being  first  formed 
from  the  chlor  acetic  acid,  the  formation  of  the  ether  may  be  represented 
as  given.  The  resulting  compound  which,  in  the  above  case,  is  an 
ether  of  di-  (hydroxy  acetic  acid)  is  known  as  di-glycolic  acid  ;  hydroxy 
acetic  acid  itself  being  glycolic  acid.  It  yields  an  anhydride  by  the 
loss  of  water  from  the  two  carboxyls. 


(HO)OC—  CH2—  O—  CH2—  COO(H)  "I!    OC—  CH2—  O—  CH2—  CO 

Di-glycolic  acid 

-  o  -  - 


Di-glycolic  acid 
anhydride 

In  this  anhydride  the  open  chain  structure  of  the  di-glycolic  acid  is 
converted  into  a  closed  ring  structure.  This  is  similar  to  the  gamma- 
anhydrides  described  below  in  (7). 

Esters  with  Acids.  —  (3)  The  hydroxy  acids  form  esters  with  other 
acids,  in  this  case  also  reacting  as  an  alcohol.  These  compounds  will 
be  mixed  esters  and  acids. 


CH3—  CO—  O(H  +  HO)—  CH2—  COOH     Z? 

Acetic  acid  Hydroxy  acetic  acid 

CH3—  CO—  O—  CH2—  COOH 

Acetyl  hydroxy  acetic  acid 

(Ester  acid) 

Esters  with  Alcohols.  —  (4)  They  form  esters  with  other  alcohols, 
in  this  case  reacting  as  an  acid.  These  compounds  are  mixed  alcohols 
and  esters  or  hydroxy  esters. 

HO—  CH2—  CO—  O(H  +  HO)—  C2H6  —  >  HO—  CH2—  CO—  O—  C2H5 

Hydroxy  acetic  acid  Ethyl  ester  of  hydroxy 

acetic  acid 

(Hydroxy  ester) 

Both  reactions  (3)  and  (4)  take  place  also  between  two  molecules  of  the 
alpha-  hydroxy  acid  itself  in  which  case  the  product  is  termed  an  anhy- 
dride as  discussed  below  in  (7). 


HYDROXY   MONOBASIC   ACIDS  241 

Ether-esters. — (5)  They  form  double  ether  and  ester  compounds  in 
which  case  they  react  as  both  alcohol  and  acid  toward  another  alcohol. 

CH2O(H  +  HO)— C2H5  CH2— O— C2H5 

I  — >         I 

CO— O(H  +  HO)— C2H5  CO— O— C2H6 

Hydroxy  acetic  Ethyl  alcohol  Ethyl  ether  and  ethyl  ester 

acid  of  hydroxy  acetic  acid 

(Ether-ester) 

Mixed  Esters. — (6)  Still  another  form  of  ester  would  be  possible, 
viz.,  one  in  which  the  hydroxy  acid  would  react  as  an  alcohol  to  another 
acid  and  as  an  acid  to  another  alcohol.  This  would  give  us  a  mixed 
alcohol-acid  ester. 

CH2— (OH  +  H)OOC— CH3  CH2— O— OC— CH3 

I  — >         I 

CO— 0(H  +  HO)— C2H5  CO— O— C2H5 

Hydroxy  acetic  Acetic  acid  Ethyl  ester  of  acetyl- 

acid  Alcohol  hydroxy  acetic  acid 

(Acid-alcohol  di-esler) 

Such  a  compound  is,  however,  not  known.  If  it  were  formed  it 
would  probably  yield  an  anhydride  by  two  molecules  losing  two  mole- 
cules of  ethyl  acetate.  The  result  would  be  the  same  as  in  the  case  of 
alpha-hydroxy  acid  anhydrides  as  in  (7). 

Anhydrides. — (7)  The  most  striking  reactions  of  the  hydroxy  acids 
are  those  in  which  the  alpha-,  beta-,  and  gamma-hydroxy  acids  react 
differently.  These  reactions  involve  the  loss  of  water  and  the  formation 
of  anhydrides.  The  reaction  takes  place  simply  under  the  influence  of 
heat,  and  shows  the  different  effect  which  is  produced  by  a  difference 
in  the  position  of  the  hydroxyl  group  in  relation  to  the  carboxyl. 

alpha-Hydroxy  Acid  Anhydrides. — When  an  a/^<z-hydroxy  acid 
is  heated,  or  when  it  simply  stands  over  sulphuric  acid,  two  molecules 
react  together  as  an  alcohol-acid  compound,  in  the  manner  described 
above  in  (3)  and  (4).  The  alcoholic  hydroxyl  of  one  molecule  reacts 
with  the  acid  hydroxyl  of  the  other  molecule  and  water  is  lost  with  the 
formation  of  a  single  anhydride  which  is  really  an  ester.  This  com- 
pound then  loses  a  second  molecule  of  water  by  the  reaction  between 
the  remaining  alcoholic  and  acid  hydroxyl  groups  forming  a  double 
anhydride  or  a  double  ester  as  discussed  above  in  (6) .  The  name  of  such 
double  anhydride  takes  the  termination  ide  in  place  of  ic  of  the  original 

16 


242  ORGANIC  CHEMISTRY 

acid.     In  it  the  open  chain  structure  of  the  original  acid  has  been  con 
verted  into  a  closed  chain  or  ring  structure. 

CH3— CH— CO  CH3— CH— CO 
(OH)    OH      _^Q  ^      (OH) 

0(H)    OH  0(H) 

OC CH— CH3  OC— CH— CH3 

a-Hydroxy-propionic  acid  Single  anhydride 

Lactic  Acid  Lactic  acid 

(2  mol.)  anhydride 

CH3— CH— CO 

I          I 

o      o 

OC CH— CH3 

Double  anhydride 
Lactide 

fo/a-Hydroxy  Acid  Anhydrides. — When  beta-hydroxy  acids  are 
heated  alone,  or  with  potassium  hydroxide,  water  is  lost  from  one  molecule. 
In  this  case  water  is  formed  from  the  alcoholic  hydroxyl  and  one  hydrogen 
from  the  neighboring  methyl  residue.  The  product  is  an  unsaturated 
acid.  From  /3-hydroxy  propionic  acid  we  obtain  acrylic  acid,  as  follows : 

CH2— CH— COOH       -H2O      CH2  =  CH— COOH 

I  — >  Acrylic  acid 

(OH      H) 

/3-Hydroxy  propionic  acid 
Hydracylic  acid 

This  reaction  is  exactly  analogous  to  that  taking  place  with  beta- 
halogen  acids  which  by  loss  of  hydrogen  halide  yield  an  unsaturated 
acid  (p.  233).  In  case  there  are  more  than  three  carbon  groups  the 
loss  of  water  is  almost  always  between  the  alpha-  and  the  beta-carbons. 
gamma-Hydroxy  Acid  Anhydrides. — When  solutions  of  gamma- 
hydroxy  acids  are  heated,  often  on  simply  standing  at  ordinary  tem- 
peratures, water  is  lost  from  one  molecule  and  anhydrides  result.  In 
the  case  of  the  beta-hydroxy  acids  the  water  is  lost  from  the  alcoholic 
hydroxyl  and  the  hydrogen  of  the  neighboring  carbon  group.  With  the 


HYDROXY   MONOBASIC   ACIDS  243 

gamma-hydroxy  acids,  however,  water  is  lost  from  the  alcoholic  and  the 
acid  hydroxyl  in  the  same  molecule,  forming  an  inner  anhydride. 

CH2— CH2— CH2— CO        CH2— CH2— CH2— CO 


(OH  H)0 


O 


•y-Hydroxy  butyric  acid  7-Hydroxy  butyric  acid  anhydride 

Butyric  lactone 

The  same  reaction  takes  place  with  the  delta-hydroxy  acids.  The 
reaction  is  analogous  to  that  in  the  case  of  the  gamma-halogen  acids 
which,  by  the  loss  of  hydrogen-halide,  form  a  similar  inner  anhydride 
compound.  These  inner-anhydrides  are  known  by  the  name  of 
lactones,  and  are  distinguished  by  the  letter  prefix  7-  or  5-,  as  the 
case  may  be.  This  ready  splitting  off  of  water  from  the  two  hydroxyl 
groups  in  the  same  molecule  will  be  made  clear  if  the  space  configuration 
of  the  molecule  of  a  gamma-hydroxy  acid  is  examined,  especially  if  a 
model  of  such  an  acid  be  made  of  tetra-hedral  carbon  groups.  Accord- 
ing to  the  tetra-hedral  theory  of  van'tHoff,  if  four  or  five  carbon  groups 
in  a  chain  have  a  hydroxyl  group  on  the  first  and  on  the  fourth  or  fifth 
carbon  these  two  hydroxyls  will  approach  very  near  to  each  other,  in 
the  case  of  a  four  carbon  compound,  and  will  practically  touch  each 
other  if  five  carbons  are  present. 

The  above  reactions  of  the  hydroxy  acids  show  plainly  the  variety  of 
products  possible  because  of  the  mixed  alcohol-acid  character  of  the 
compounds  and  the  readiness  with  which  these  two  kinds  of  groups 
react  either  with  themselves,  with  each  other  or  with  other  reagents. 
We  shall  find  in  the  study  of  the  amino  acids  that  alpha-,  gamma-,  and 
delta-a,mino  acids  have  this  same  tendency  to  form  anhydrides.  In 
this  case  water  is  lost  from  the  acid  hydroxyl  and  one  of  the  hydrogens 
of  the  amino  group,  the  imino  group,  ( — NH — ),  acting  as  the  uniting 
link,  like  the  oxygen  in  the  above  cases.  The  conversion  of  gamma-  or 
delta-hydroxy  acid  or  amino  acid  open  chain  compounds  into  closed 
ring  or  cyclic  compounds  is  of  great  significance  in  connection  with  the 
relation  between  the  two  classes  of  compounds. 

Reduction. — (8)  When  hydroxy  acids  are  treated  with  hydrogen 
iodide  they  are  readily  reduced  to  the  unsubstituted  acid.  In  other 
words,  the  hydroxyl  group  is  reduced  to  hydrogen.  In  this  reaction 
the  hydroxyl  group  is  first  replaced  by  iodine  giving  the  iodine  sub- 
stituted acid.  This  is  then  reduced  because  of  the  strong  reducing 


244  ORGANIC  CHEMISTRY 

power  of  hydrogen  iodide.  With  hydrogen  bromide,  which  is  not  so 
strong  a  reducing  agent,  the  reaction  stops  with  the  halogen  substituted 
acid.  The  reaction  takes  place  especially  with  the  poly-hydroxy  acids. 

CH2(OH)— CH(OH)— CH(OH)— COOH     +      6HI    > 

a-/S-X-Tri-hydroxy  butyric 
acid 

CH3— CH2— CH2— COOH  +  sH2O  +  3X2 

Butyric  acid 

This  is  an  important  reaction  for  converting  the  poly-hydroxy  acids 
into  simpler  acids. 

Hydroxy  Formic  Acid  HO— COOH 

While  hydroxy  formic  acid  is  the  simplest  of  the  hydroxy  mono- 
carboxy  acids  it  will  not  be  discussed  here  because,  as  may  be  seen  if 
the  formula  is  examined,  it  corresponds  to  the  hypothetical  carbonic 
acid,  H2C03. 

H— COOH  HO— COOH  H2CO3 

Formic  acid  Hydroxy  formic  acid  Carbonic  acid 

As  hydroxy  formic  acid  is  undoubtedly  identical  with  carbonic*  acid  it 
will  be  studied  later  as  the  latter  compound  (p.  425). 

Hydroxy  Acetic  Acid  CH2(OH)— COOH 

The  next  higher  hydroxy  acid  is  hydroxy  acetic  acid  CH2(OH) — 
COOH,  known  also  as  glycolic  acid.  It  may  be  prepared  (a)  from 
chlor  acetic  acid,  (b)  from  the  cyan-hydrine  obtained  from  formic  alde- 
hyde, or  (c)  by  the  oxidation  o£  ethylene  glycol,  by  reactions  which  have 
been  already  discussed.  Its  relation  to  ethylene  glycol  gives  it  the 
name  of  glycolic  acid.  It  may  be  considered  as  a  direct  oxidation 
product  of  ethane. 

CH3  CH2OH  CH2OH  CH2OH  CH2OH 

I  I  I  I  I 

CH3  CH3  CH2OH  CHO  COOH 

Ethane  Ethyl  alcohol  Glycol  Glycolic  aldehyde         Glycolic  acid 

Glycolic  acid  is  a  crystalline  solid  melting  at  79°-8o°,  and  is  easily 
soluble  in  water.  It  forms  an  anhydride,  ethers  and  esters  as  has  been 
explained  for  hydroxy  acids  in  general.  As  there  are  only  two  carbon 
atoms  present  no  other  hydroxy  acetic  acid  is  possible.  The  double 
anhydride  of  glycolic  acid  is  known  as  glycolide  and  is  obtained  when 


HYDROXY   MONOBASIC   ACIDS  245 

glycolic  acid  is  heated.  It  is  isomeric  with  di-glycolic  acid  anhydride 
(p.  240).  The  difference  in  these  two  isomers  is  plainly  shown  in 
their  structural  formulas  and  in  their  formation  from  glycolic  acid. 

CH2(OH         H)O— CH2  -2H2O          CH2-O-CH2 

I  +  I  II 

COO(H          HO)   OC  CO  -O-CO 

Glycolic  acid  Di-glycolic  acid  anhydride 

CH2-(OH         H)O- OC        -2H2O          CH2-O-CO 

I  +  !  II 

CO-0(H          HO)-H2C  CO  -0-CH2 

Glycolic  acid  Glycolide 

Both  are  obtained  from  two  molecules  of  glycolic  acid  by  the  loss  of  two 
molecules  of  water.  In  di-glycolic  acid  anhydride  one  molecule  of  water 
is  formed  from  the  two  alcohol  hydroxyls  and  one  from  the  two  acid 
hydroxyls.  In  glycolide  each  molecule  of  water  is  formed  from  one 
alcohol  hydroxyl  and  one  acid  hydroxyl.  The  first  is  an  anhydride  of  an 
ether-acid,  di-glycolic  acid,  while  glycolide  is  a  double  ester  of  an  alcohol- 
acid. 

Hydroxy  Propionic  Acids 
Hydracrylic  acid  CH2OH — CH2 — COOH       /3-Hydroxy  propionic  acid 

Propionic  acid  plainly  yields  two  isomeric  hydroxy  acids,  viz., 
an  alpha-  and  a  fo/a-acid.     The  constitution  of  the  two  compounds  is, 

CH3-  CH(OH)  -  COOH        a-Hydroxy  propionic  acid 
CH2(OH)-CH2-COOH      /3-Hydroxy  propionic  acid 

We  have  just  spoken  of  the  different  action  of  the  alpha-,  beta-,  and 
gamma-halogen  acids  toward  alkalies  (p.  233),  and  of  the  similar 
different  action  of  the  alpha-,  beta-,  and  gamma-hydroxy  acids  when 
dehydrated  (p.  241).  The  second  of  the  above  acids,  viz.,  the  /5- 
hydroxy  propionic  acid,  shows  the  reaction  characteristic  of  beta-adds. 
On  heating,  or  by  the  action  of  sulphuric  acid,  it  loses  water  and  is 
converted  into  the  corresponding  ethylene  unsaturated  acid,  propenoic 
acid,  as  follows: 

CH2  -  CH  -  COOH  -  H2O 

|  -^H  CH2=CH-COOH 

(OH      H)  +H20 

Hydracrylic  acid 
/3-Hydroxy  propiQttiQ  acid 


246  ORGANIC  CHEMISTRY 

Propenoic  acid  is  commonly  known  as  acrylic  acid  (p.  172),  and 
jS-hydroxy  propionic  acid  is  therefore  named  hydracrylic  acid,  i.e., 
hydrated  acrylic  acid. 

Synthesis  from  Acrylic  Acid. — Three  methods  of  synthesis  of  hydra- 
crylic acid  show  its  relation  to  acrylic  acid,  to  propionic  acid  and  to 
ethylene.  When  acrylic  acid  is.  heated  with  sodium  hydroxide  to  100° 
it  takes  up  a  molecule  of  water  and  yields  hydracrylic  acid.  The  reac- 
tion is  simply  the  reverse  of  the  one  above. 

From  Propionic  Acid. — The  simplest  method  of  synthesis  is  the  one 
which  shows  the  relation  of  hydracrylic  acid  to  propionic  acid  and 
proves  that  it  is  the  beta-hydroxy  acid.  When  j8-iodo  propionic  acid  is 
boiled  with  water,  or  with  aqueous  silver  hydroxide,  hydracrylic  acid  is 
obtained. 

I-CH2-CH2— COOH+H-OH     (or  AgOH)     — * 

/3-Iodo  propionic  acid 

HO-CH2-CH2-COOH 

/3-Hydroxy  prppionic  acid 
Hydracrylic  acid 

Frorn^Ethylene. — The  reverse  of  this  reaction  takes  place  when 
hydracrylic  acid  is  treated  with  hydrogen  iodide,  HI,  as  discussed 
above  in  (8).  The  third  synthesis  of  hydracrylic  acid  shows  its  relation 
to  ethylene.  Ethylene  takes  up,  by  addition,  hypochlorous  acid, 
HO  — Cl,  in  just  the  same  way  as  it  does  bromine  or  hydrobromic  acid. 
The  compound  obtained  is  glycol  chlor  hydrine.  This  chlor  hydrine, 
by  treatment  with  potassium  cyanide,  is  converted  into  the  glycol 
cyan  hydrine.  The  cyan  hydrine,  being  an  acid  nitrile,  yields  an  acid 
on  hydrolysis.  The  acid  obtained  is  hydracrylic  acid. 

CH2  CH2OH 

||         +     HO-C1       -*  +     K-CN > 

CH2  CH2C1 

Ethylene  Glycol  chlor 

hydrine 

CH2OH  CH2OH 

|  +     2H20       --*      | 

CH2CN  CH2-COOH 

Glycol  cyan  Hydracrylic  acid 

hydrine 

Lactic  Acid     CHg— CH(OH)— COOH     a-Hydroxy  Propionic  Acid 

The  isomeric  alpha-hydroxy  acid  is  prepared  from  a-iodo  propionic 
acid  in  exactly  the  same  way  as  the  beta-acid  is  prepared  from  the  beta- 


HYDROXY   MONOBASIC   ACIDS  247 

iodo  compound.  The  reverse  reaction,  viz.,  the  conversion  of  the 
alpha-hydroxy  acid  into  the  alpha-iodo  acid,  also  takes  place. though 
in  this  case  action  goes  further  and  the  unsubstituted  propionic  acid  is 
obtained  as  in  (8)  above.  Both  of  these  reactions  prove  the  constitu- 
tion of  the  compound. 

+  AgOH 
CH3-CHI-COOH          -^H         CH3-CH(OH)-COOH 

a-Iodo  propionic  acid  _i_  TTJ  a-Hydroxy  propionic  acid 

The  synthesis  from  acet-aldehyde  also  proves  this  constitution. 
By  the  addition  of  hydrogen  cyanide  acet-aldehyde  yields  a  cyan 
hydrine  in  which  the  hydroxyl  and  cyanogen  groups  are  linked  to  the 
same  carbon.  This  cyan  hydrine,  like  glycol  cyan  hydrine,  being  an 
acid  nitrile,  yields  an  acid  on  hydrolysis.  The  acid,  so  obtained  is 
lactic  acid  which  therefore  must  be  an  alpha-hydroxy  acid  containing 
three  carbon  atoms,  i.e.,  a-hydroxy  propionic  acid. 

H  H 

I  ! 

CH3-C  =  0   +    H-CN       -*     CH3-C-CN  +  2H2O       — » 

Acet-aldehyde 

OH 

Acid  nitrile 

H 

I 
CH3-C-COOH 

OH 

a-Hydroxy    propionic  acid 
Lactic  acid 

This  alpha-acid  is  of  much  greater  importance  than  the  isomeric 
beta-add,  hydracrylic  acid.  It  is  commonly  known  as  lactic  acid  and 
occurs  in  nature,  being  present  in  sour  milk  where  it  is  produced  by  the 
acid  fermentation  of  milk-sugar  due  to  bacterial  action.  Considering 
both  the  carboxyl  and  hydroxyl  as  substituting  groups  these  two  acids 
may  be  considered  as  di- substituted  ethanes.  As  such  the  beta-acid 
has  the  ethylene  or  symmetrical  structure  and  the  alpha-acid  has  the 
ethylidene  or  un symmetrical  structure.  On  this  account  the  former  is 
sometimes  called  ethylene  lactic  acid  and  the  latter,  ethylidene  lactic 
acid.  The  names  are  not,  however,  good  as  the  beta-acid,  hydracrylic 
acid,  is  in  no  sense  a  lactic  acid. 


248  ORGANIC  CHEMISTRY 

Reactions.  Anhydrides. — The  most  important  reaction  of  lactic 
acid  is  its  formation  of  anhydrides.  As  explained  previously  (p.  241) 
for  a/^Aa-hydroxy  acids  in  general,  the  anhydrides  formed  are  two. 
The  first,  known  as  lactic  acid  anhydride,  is  formed  by  the  loss  of  one 
molecule  of  water  from  two  molecules  of  the  acid.  The  second  is  a 
closed  ring  compound,  or  inner  anhydride,  and  is  known  as  lactide,  being 
analogous  to  glycolide.  It  is  formed  by  the  loss  of  two  molecules  of 
water  from  two  molecules  of  the  acid  or  by  the  loss  of  one  more 
molecule  of  water  from  the  single  anhydride.  Lactic  acid  anhydride, 
the  first  compound,  is  produced  by  heating  the  acid  to  i3O°-i4O°,  or 
even  at  ordinary  temperatures  in  dry  air.  It  is  an  easily  soluble  amor- 
phous compound.  The  lactide  is  obtained  by  passing  dry  air  through 
lactic  acid  heated  to  150°.  It  is  an  almost  insoluble  crystalline  sub- 
stance melting  at  255°. 
CH3— CH— COOH  _H20  CH3— CH COO(H)  _^o 

(OH)        OH  O  (OH) 

(H)~ O— OC— CH— CH3  — OC— CH— CH, 

2  Mol.  lactic  acid  Lactic  acid  anhydride 

CH3— CH CO— 


O  O 


CH— CH3 

Lactide 

Pyro-racemic  Acid. — By  oxidation  lactic  acid  has  the  secondary 
alcohol  group  converted  into  a  carbonyl  group  yielding  a  ketone  acid 
known  as  pyro-racemic  acid  (p.  253). 
CH3— CH(pH)  -COOH     +     O        >        CH3— CO— COOH 

Lactic  acid  Pyro-racemic  acid 

When  heated  with  dilute  sulphuric  acid  lactic  acid  is  split  into  acet- 
aldehyde  and  formic  acid.     The  reaction  resembles  the  reverse  of  the 
reaction  of  its  formation  from  acet-aldehyde  through  the  cyan  hydrine. 
H  H 

I  I! 

CH3— C— (COOH)        >        CH3— C  =  O    +    H— COOH 

Acet-aldehyde  Formic  acid 

0(H) 

Lactic  acid 


HYDROXY   MONOBASIC   ACIDS 


249 


CH3— CH(OH)— COO— C2H5 

Ethyl  ester  of  lactic  acid 


By  bacterial  fermentation  the  calcium  salt  of  lactic  acid  is  decomposed 
into  salts  of  simpler  acids,  e.g.,  propionic,  butyric  and  valeric.  As  an 
acid  lactic  acid  yields  an  ethyl  ester  with  ethyl  alcohol  and  as  an  alcohol 
it  yields,  with  acetic  anhydride,  an  acetyl  derivative.  The  latter  com- 
pound results  from  the  putrefaction  of  muscular  tissue,  as  this  contains 
both  lactic  and  acetic  acid. 

CH3— CH(OOC— CH3)— COOH 

^^__~v,,  -,—LS—*—  Acetyl  lactic  acid 

Stereo-isomerism. — In  addition,  however,  to  the  two  structurally 
isomeric  acids  which  we  have  been  considering,  one  being  an  alpha- 
hydroxy  acid,  the  other  a  beta-hydroxy  acid,  there  are  known  two  other 
acids  of  the  same  composition  both  of  which  prove  to  be  a-hydroxy 
propionic  acid.  Of  these  three  alpha-adds  two  are  optically  active, 
one  being  dextro-  and  the  other  /ezw-rotatory.  The  third  is  optically 
inactive  but  resolvable  into  its  optical  components.  An  examination 
of  the  formula  of  a-hydroxy  propionic  acid  shows  that  it  contains  an 
asymmetric  carbon  atom. 

H 

I 
CH3— CH(OH)— COOH    or     CH3— C— COOH 


a-Hydroxy  propionic  aeid 


OH 

Lactic  acid 


CH. 


COOH 


H 


rOOH 


OH 


levc> 


*  •  !*• 

inactive 
Lactic  actd 


FIG.  4. 


250  ORGANIC  CHEMISTRY 

The  existence  of  three  stereo-isomeric  lactic  acids  is  therefore  explained 
in  exactly  the  same  way  as  the  three  stereo-isomers  in  the  case  of 
active  amyl  alcohol,  2-methyl  butanol-i  (p.  90).  We  need  not  repeat 
the  discussion  of  stereo-isomerism  as  explained  by  the  van't  Hoff-LeBel 
theory  of  the  asymmetric  carbon  atom,  i.e.,  the  tetra-hedral  theory. 
The  discussion  as  previously  given  for  the  amyl  alcohols,  applies  exactly 
in  the  present  case. 

Inactive  or  Fermentation  Lactic  Acid. — Lactic  acid  was  discovered 
by  Scheele,  in  sour  milk,  in  1780.  The  souring  of  milk  is  caused  by 
this  formation  of  lactic  acid,  producing  the  result  known  as  curdling 
which  is  the  coagulation  of  the  milk  protein  casein.  The  lactic  acid  is 
formed  by  the  bacterial  fermentation  of  the  milk  sugar  present  in  the 
milk  and  the  stereo-isomeric  variety  thus  formed  is  the  one  that  is 
optically  inactive.  Inactive  lactic  acid  is  thus  also  known  as  lactic  acid 
of  fermentation  or  simply  as  ordinary  lactic  acid.  It  may  also  be 
produced  by  the  action  of  certain  bacteria  upon  glucose  or  upon  cane 
sugar  and  by  the  action  of  alkalies  upon  substances  containing  sugar, 
especially  if  considerable  invert  sugar  is  present,  as  in  the  case  of 
molasses.  Commercially  lactic  acid  is  made  from  the  whey  of  milk 
left  after  the  cheese  curd  has  been  removed.  This  whey  contains  all 
of  the  milk  sugar  of  the  milk.  Also  the  molasses  left  after  the  greater 
part  of  the  milk  sugar  has  been  crystallized  out  is  used.  Other  com- 
mercial sources  of  lactic  acid  are  cane  sugar  and  glucose  sugar  that  has 
been  made  by  the  hydrolysis  of  starch.  In  all  of  these  cases  in  which 
sugar  is  fermented  lactic  acid  bacteria  are  added  in  the  form  of  sour 
milk,  putrid  cheese  or  pure  cultures.  Ordinary  lactic  acid  is  a  colorless 
thick  liquid  boiling  at  120°,  (12  mm.),  and  with  a  specific  gravity  of 
i. .248.  It  is  difficult  to  obtain  it  pure  as  it  always  contains  more  or 
less  anhydride.  The  purest  usually  obtained  is  about  80  per  cent  and 
has  a  specific  gravity  of  1.21.  The  chief  uses  of  lactic  acid  are  in 
medicine,  in  the  form  of  salts,  and  in  dyeing  and  tanning.  The  most 
common  salts  are  the  calcium,  zinc  and  iron  lactates.  Like  other 
inactive  asymmetric  compounds  inactive  lactic  acid  may  be  split  into 
its  optical  components,  i.e.,  the  dextro  and  the  levo  lactic  acids.  The 
strychnine  salt  is  the  salt  used  for  this  splitting. 

Dextro  Lactic  Acid  or  Sarco-lactic  Acid. — Dextro  lactic  acid  is 

found  in  muscular  tissue  and  on  this  account  it  is  known  as  sarco-lactic 

•  acid.     It  is  also  known  as  para-lactic  acid.     It  was  discovered  by  Liebig 


ALDEHYDE  ACIDS  AND  KETONE  ACIDS          251 

in  the  juices  of  flesh  and  is  present  in  meat  extracts.  It  is  found  norm- 
ally in  blood  and  in  urine.  It  is  also  produced  by  the  fermentation 
of  the  sugars  previously  mentioned  by  the  action  of  specific  bacteria. 
It  resembles  the  inactive  lactic  acid  in  all  of  its  properties  except  its 
optical  activity.  It  forms  anhydrides  less  easily  than  the  inactive  acid. 
Its  zinc  salt  is  more  soluble  and  its  calcium  salt  less  soluble  than  the 
same  salts  of  the  inactive  acid.  An  interesting  fact  is  that  the  salts  of 
dextro  lactic  acid  are  lew  rotatory.  The  anhydride  is  also  levo  rotatory 
and  by  heating  is  converted  into  the  anhydride  of  the  inactive  lactic  acid. 

Levo  Lactic  Acid. — Levo  lactic  acid  was  first  obtained  by  the  fer- 
mentation of  cane  sugar  by  specific  bacteria.  It  is  levo  rotatory  but, 
like  the  dextro  acid,  the  rotation  of  its  salts  and  its  anhydride  is  reversed, 
being  dextro  rotatory.  The  levo  lactic  acid  and  also  the  dextro  acid 
may  be  obtained  by  splitting  the  inactive  acid  into  its  optical  compo- 
nents by  means  of  its  strychnine  salt. 

In  addition  to  being  present  in  sour  milk  lactic  acid  is  found  in 
ensilage,  in  sauer-kraut  and  in  various  liquids  and  tissues  of  the  human 
body,  e.g.,  gastric  juice,  the  fermented  juice  of  muscle,  the  brain,  the 
blood  and  the  urine.  In  most  of  its  occurrences  in  the  human  body  it 
is  the  dextro  lactic  acid  which  is  present.  In  these  cases  it  is  probably 
the  result  of  the  fermentation  of  sugars.  The  occurrence  of  lactic  acid 
in  the  human  body  is  of  great  physiological  importance.  It  has  been 
found  that  it  is  connected  with  muscular  and  nervous  fatigue  and  with 
the  oxidation  of  glucose  in  the  cells.  In  connection  with  its  formation 
by  the  fermentation  of  sugars  it  is  probable  that  it  is  an  intermediate 
product  in  the  alcoholic  fermentation  of  sugars. 

III.  ALDEHYDE  ACIDS  AND  KETONE  ACIDS 

This  group  of  mixed  substitution  products  embracing  compounds 
that  are  both  aldehyde  or  kef  one  and  acid  in  character  are  directly  related 
to  the  mixed  alcohol  and  acid  compounds.  If  a  hydroxy  acid  contain- 
ing a  primary  alcohol  group  has  this  group  oxidized  the  first  product 
will  be  an  aldehyde  acid.  Similarly  if  the  alcohol  group  is  a  secondary 
one  the  oxidation  product  will  be  a  ketone  acid. 

CH2OH— COOH  +  O        >        CHO— COOH 

Glycolic  acid  Glyoxylic  acid 

(Primary)  Hydroxy  acid  Aldehyde  acid 

CH3— CHOH— CH2— COOH  +  O       — »     CH3— CO—  CH2— COOH 

/3-Hydroxy  butyric  acid  Aceto  acetic  acid 

(Secondary)  Hydroxy  acid  Ketone  acid 


252  ORGANIC  CHEMISTRY 

ALDEHYDE  ACIDS 
Glyoxylic  Acid       CH(OH)2— COOH      or      CHO— COOH 

This  acid  may  be  prepared  by  the  oxidation  of  glycolic  acid  as  above 
but  better  from  di-brom  acetic  acid  by  the  action  of  water.  These 
reactions  are  analogous  to  the  preparation  of  acetic  aldehyde  by 
the  oxidation  of  ethyl  alcohol  and  by  the  action  of  water  upon  un- 
symmetrical  di-brom  ethane  (p.  115).  In  both  of  these  latter  cases 
the  reaction  has  been  represented  as  taking  place  with  the  formation 
of  an  unstable  intermediate  product  containing  two  hydroxyl  groups 
linked  to  one  carbon  atom  which  by  loss  of  water  yields  the  aldehyde. 
In  glyoxylic  acid,  however,  we  have  evidence  that  this  intermediate 
product  is  the  stable  compound,  for  the  composition  of  it  corresponds 
to  the  formula  HOOC— CHO.H2O  or  HOOC— CH(OH)2.  It  is  im- 
possible to  drive  off  this  extra  H2O  without  decomposing  the  compound. 
It  will  be  recalled  also  that  in  chloral  hydrate  we  have  the  same  facts 
in  regard  to  the  composition  of  this  compound  though  in  this  case  the 
water  may  be  driven  off  leaving  a  stable  compound,  chloral.  Placing 
these  three  compounds,  viz.,  acet-aldehyde,  chloral  hydrate  and  gly- 
oxylic acid,  together  we  can  see  the  similarity  and  relation. 

-H2O 
CH3— CH2OH  +  0         — >      CH3— CH(OH)2          -t      CH3— CHO 

Ethyl  alcohol  Di-hydroxy  compound  Acet-aldehyde 

(Unstable)  (Stable) 

-H2O 
CC13— CH(OH)2          —      CC13— CHO 

Chloral  hydrate  Chloral 

Di-hydroxy  compound  (Stable) 

(Stable) 

-H2O 
HOOC— CH2OH  +  O  >  HOOC— CH(OH2) »  HOOC— CHO 

Glycolic  acid  Glyoxylic  acid  Glyoxylic  acid 

Di-hydroxy  compound  Aldehyde  acid 

(Stable)  (Unstable) 

Now  in  both  glyoxylic  acid  and  chloral  hydrate  the  carbon  atom  holding 
the  two  hydroxyl  groups  is  linked  to  a  strongly  negative  carbon  group, 
viz.,  (CC13 — )  or  ( — COOH),  and  it  is  thought  that  this  condition  gives 
stability  to  the  two  hydroxyl  groups  linked  to  one  carbon  atom.  We  shall 
find  later  (p.  297)  in  the  case  of  mesoxalic  acid  that  the  same  condition 
exists.  We  may  say,  therefore,  that  while  the  evidence  is  not  absolutely 
conclusive  yet  it  indicates  that  in  glyoxylic  acid  we  have  a  di-hydroxy 
compound  in  accordance  with  its  composition  and  the  composition  of  its 


ALDEHYDE  ACIDS  AND  KETONE  ACIDS          253 

salts.     Reactions  with  phenyl  hydrazine  and  hydroxyl  amine  indicate, 
however,  that  it  has  the  aldehyde  constitution. 

Formyl  Acetic  Acid       H— CO— CH2— COOH 

This  acid  may  be  considered  as  a  homologue  of  glyoxylic  acid  but  as 
it  is  really  a  ketone  acid  in  its  formation  and  reactions  it  will  be  men- 
tioned a  little  later. 

Glucuronic  Acid  or  Glycuronic  Acid       CHO — (CHOH)  4— COOH 

This  acid  is  a  six  carbon  tetra-hydroxy  aldehyde  acid  related  to  glu- 
cose sugar  and  will  be  mentioned  here  by  name  only. 

KETONE  ACIDS 

The  ketone  acids  are  a  much  more  important  group  than  the  alde- 
hyde acids  and  have  been  of  especial  value  in  synthetic  reactions. 
Though  they  are  quite  numerous  there  are  none  that  are  of  important 
natural  occurrence.  Our  present  study  will  involve  the  consideration 
in  detail  of  only  two  of  them  as  with  these  two  we  can  explain  their 
relationship  and  constitution  and  the  important  reactions  which  they 
undergo.  They  are  grouped  into  classes  depending  upon  the  position 
which  the  ketone  carbonyl  group  occupies  in  relation  to  the  acid  carboxyl 
group,  i.e.,  they  are  designated  as  alpha-ketone  acids,  etc. 

Pyro-racemic  Acid       CHg— CO— COOH.    Pyruvic  Acid 

Synthesis  from  Acetyl  Chloride. — As  can  be  readily  seen  this  is  the 
simplest  ketone  acid  that  is  possible  and  it  is  an  alpha-ketone  acid. 
Its  name  is  derived  from  the  fact  that  it  is  obtained  from  racemic  acid 
by  heat.  It  is  a  liquid  boiling  at  165°.  Its  constitution  is  best  shown 
by  the  following  syntheses.  Acetyl  chloride  by  means  of  silver  cyanide 
yields  acetyl  cyanide  which  by  hydrolysis  gives  pyro-racemic  acid. 

CH3+CO—  (Cl+Ag)— CN »AgCl+CH3—  CO—  CN+2H2O > 

Acetyl  chloride  Acetyl  cyanide 

CH3— CO— COOH+NH3 

Pyro-racemic  acid 

From  a-a-Di-brom  Propionic  Acid. — Di-brom  propionic  acid  with 
both  bromine  atoms  in  the  alpha  position  yields  pyro-racemic  acid  by 
treatment  with  silver  oxide. 

CH3— CBr2— COOH  +  AgO    >     CH3— CO— COOH  +  2AgBr 

a-a-Di-brom  propionic  acid  Pyro-racemic  acid 


254  ORGANIC  CHEMISTRY 

From  Lactic  Acid. — When  lactic  acid,  a-hydroxy  propionic  acid,  is 
oxidized  pyro-racemic  acid  is  obtained  as  was  recently  stated  (p.  248). 
Also  pyro-racemic  acid  may  be  reduced  to  lactic  acid. 

+  0 

Lactic  acid  CH3—  CH(OH)— COOH    "H    CH3— CO-COOH 

-f H         Pyro  -racemic  acid 

Physiologically  pyruvic  acid  is  associated  with  lactic  acid  and  glucose  in 
the  oxidation  of  the  latter  in  the  cells. 

From  Acetic  and  Formic  Acids. — A  fourth  method  of  synthesis  from 
acetic  and  formic  acid  esters  will  be  explained  in  detail  in  connection 
with  the  next  acid.  All  of  these  syntheses  prove  the  constitution  of 
pyro-racemic  acid  as  an  alpha-ketone  acid  as  given.  It  may  be  con- 
sidered as  aceto  formic  acid  which  is  in  accord  with  the  fourth  method  of 
synthesis.  As  an  acid  it  forms  all  acid  derivatives  and  as  a  ketone  it 
undergoes  the  characteristic  ketone  reactions,  e.g.,  with  phenyl  hydra- 
zine  and  hydroxyl  amine.  On  heating  to  150°  with  dilute  sulphuric 
acid  in  a  sealed  tube  it  loses  carbon  dioxide  and  yields  acet  aldehyde. 

CH3— CO— (COO)H    >    CH3— CHO 

Pyro-racemic  acid  Acet-aldehyde 

This  reaction  is  analogous  to  the  formation  of  methane  from  acetic 
acid  (p.  7). 

Aceto  Acetic  Acid       CH3— CO— CH2— COOH 

This  corresponds  to  pyro-racemic  acid  in  being  the  simplest  beta- 
ketone  acid  possible.  While  it  is  known  in  the  free  state  as  an  easily 
decomposed  hygroscopic  syrup  its  principal  form  is  as  the  ethyl  ester, 
CH3-CO-CH2-COOC2H5,  ethyl  aceto  acetate.  In  this  form  it  is 
prepared  and  in  this  form  it  is  used  as  a  synthetic  reagent.  '  The  ester 
is  a  colorless  liquid  boiling  at  181°,  with  a  characteristic  fruity  odor. 

Preparation  of  Ethyl  Aceto  Acetate. — Ethyl  aceto  acetate  is  made 
by  the  action  of  metallic  sodium  upon  ethyl  acetate.  The  reaction 
may  be  represented  in  its  simplest  form  as  follows: 

CH3-CO(OC2H5  +  H)-CH2-COOC2H5  +  Na    > 

Ethyl  acetate 

CH3-CO-CH2  — COOC2H5  +  C2H5ONa  +  H 

Ethyl  aceto  acetate 

While  this  reaction  represents  truly  the  beginning  and  end  products  it 
has  been  shown  by  Claisen  and  others  that  it  takes  place  in  several  steps 


ALDEHYDE  ACIDS  AND  KETONE  ACIDS  255 

and  that  the  presence  of  sodium  ethylate  is  essential.  A  little  alcohol 
present  in  the  ethyl  acetate  reacts  with  the  sodium  forming  sodium 
ethylate,  but  if  the  ethyl  acetate  has  been  purified  so  that  it  is  free  from 
alcohol  then  the  reaction  does  not  proceed  except  at  higher  tempera- 
tures and  then  very  slowly.  The  sodium  ethylate  reacts  with  the 
ethyl  acetate  forming  an  addition  product  which  is  a  mixed  sodium  salt 
and  ethyl  ester  of  normal  or  tri-hydroxy  acetic  acid. 

O  OC2H5 

CH3— C— OC2H5     +     C2H5-ONa    >     CH3— C— OC2H5 

Ethyl  acetate  Sodium  ethylate  I 

ONa 

This  is  analogous  to  the  relation  between  acids  and  the  so-called  normal 
acids  and  gives  support  to  the  idea  that  normal  carboxy  acids  are  tri- 
hydroxy  compounds. 

O  OH 

II  +H20 

CH3— C— OH  ZI        CH3— C— OH 


Acetic  acid  TT  r\ 


OH 

Normal  acetic  acid 
Tri-hydroxy  ethane 


This  addition  product  formed  from  ethyl  acetate  and  sodium  ethylate 
now  reacts  with  a  second  molecule  of  ethyl  acetate  losing  two  molecules 
of  ethyl  alcohol  and  forming  the  sodium  salt  of  ethyl  aceto  acetate  which 
on  acidifying  yields  the  free  ester. 

The  ethyl  alcohol  formed  as  the  other  product  reacts  with  sodium 
yielding  more  sodium  ethylate  and  the  reaction  continues. 

(OC2H5  H) 

I  -2C2H5OH 

CH3— C— (OC2H5  +  H)— CH— COOC2H5  — -* 


Ethyl  acetate 


ONa 

Addition  product 

ONa 


CH3— C  =  CH— COOC2H5  +  HC1 

Sodium  salt 


256  ORGANIC  CHEMISTRY 

OH 

I 
CH3— C  =  CH— COOC2H5      or      CH3— CO— CH2— COOC2H5 

Enol  formula  Ethyl  aceto  acetate  Keto  formula 

This  reaction,  however,  yields  a  compound  containing  a  hydroxyl  group 
instead  of  a  carbonyl  group  and  the  question  is  which  is  the  true  formula 
and  which  represents  the  constitution  of  aceto  acetic  ester?  The 
answer,  strange  as  it  may  seem,  is  that  both  are  right  for  we  have 
reactions  some  of  which  prove  one  and  some  the  other  constitution. 

Tautomerism. — This  brings  us  to  the  discussion  of  a  new  phenome- 
non known  as  tautomerism  which,  though  similar  to  isomerism,  is  yet 
distinct  from  it.  In  the  case  we  are  discussing  the  two  formulas  do 
not  represent  different  compounds  but  the  same  compound.  Under 
certain  conditions  with  certain  reagents  one  constitution^  holds  true, 
while  under  other  conditions  and  with  other  reagents,  the  other  formula 
represents  the  constitution.  The  fact  has  been  well  demonstrated  by 
physical  chemical  study  that  both  forms  exist  at  the  same  time  in 
equilibrium.  This  condition  of  equilibrium  varies  and  may  be  affected 
by  reagents  so  that  by  changing  the  conditions  or  the  reagents  the 
amount  of  either  form  may  be  increased  or  diminished,  the  compound 
reacting  as  though  it  was  of  one  form  only.  This,  then,  is  what  is 
termed  tautomerism  and  the  two  forms  are  known  as  tautomeric  forms . 

Enol  and  Keto. — The  formula  containing  the  hydroxyl  group  is 
termed  the  enol  form  while  the  one  with  the  carbonyl  group  is  known 
as  the  keto  form. 

Ketone  Hydrolysis. — The  reactions  of  ethyl  aceto  acetate  are  im- 
portant and  lead  to  the  extensive  use  of  the  compound  as  a  synthetic 
reagent.  With  water  in  the  presence  of  alkali  or  acid  two  distinctly 
different  hydrolyses  take  place.  When  boiled  with  dilute  alkali  or 
dilute  acid  hydrolysis  with  loss  of  carbon  dioxide  occurs  as  follows: 

H  OH     (dil.  alk.  or  acid) 

CH3— CO— CH2—  COO—  C2H5  — > 

Ethyl  aceto  acetate  -f  i  water  Ketone  hydrolysis 

CH3— CO— CH3  +  C2HbOH  +  CO2 

Acetone  Alcohol 

The  product  is  acetone,  a  ketone,  and  this  decomposition  is  known  as 
the  ketone  hydrolysis. 


ALDEHYDE  ACIDS  AND  KETONE  ACIDS  257 

Acid  Hydrolysis. — When  concentrated  alkali  or  alcoholic  alkali  is 
used  the  hydrolysis  takes  place  differently. 

(Cone,  alkali) 


CH3— CO|— CH2— COO 
HO|— H  H 


— C2H{ 
—OH 


Acid  hydrolysis 


Ethyl  aceto  acetate  +  2  water 

CH3— COOH  +  CH3— COOH  +  C2H5— OH 

Acetic  acid  Alcohol 

The  product  here  is  an  acid  and  the  reaction  is  termed  the  acid  hydroly- 
sis. Both  of  these  hydrolyses  are  more  easily  explained  by  the  keto 
constitution  for  the  ethyl  aceto  acetate. 

Sodium  Salt. — The  most  characteristic  reactions  of  the  compound 
are  the  formation  of  a  sodium  salt  and  the  subsequent  reactions  of  this 
salt. '  In  the  synthesis  from  ethyl  acetate  and  sodium  (sodium  ethylate) 
the  sodium  salt  is  the  form  in  which  the  compound  is  obtained  prior  to 
acidifying.  The  sodium  salt  may  also  be  prepared  from  the  free  ester 
by  treating  with  sodium  ethylate.  The  formation  of  such  a  metal 
salt  in  which  the  sodium  has  replaced  a  hydrogen  atom  seems  to  indicate 
the  presence  of  a  hydroxyl  group.  This  supports  the  hydroxy  or  enol 
form,  the  salt  being  CH3— C(ONa)  =  CH— COOC2H5.  The  reactions 
of  this  salt,  however,  seem  to  indicate  the  keto  form  as  the  true  con- 
stitution. The  formula  for  the  salt  in  this  form  is  CH3 — CO — CHNa — 
COOC2H5.  Such  replacement  of  a  hydrogen  in  a  hydrocarbon  residue 
by  a  metal  is  not  usual  but  in  this  case  and  in  the  case  of  malonic  acid 
(p.  275),  when  a  methylene  group,  ( — CH2 — •),  is  linked  between  two  car- 
bonyl  groups,  the  hydrogens  take  on  acid  properties  and  are  replaceable  by 
metals,  e.g.,  sodium. 

Alkyl  Derivatives. — When  this  sodium  salt  reacts  with  an  alkyl 
halide  the  reaction  is  analogous  to  the  Wurtz  reaction,  the  sodium  is 
exchanged  for  the  alkyl  radical,  and  an  alkyl  derivative  of  the  ester  is 
obtained. 

CH3— CO— CH— COOC2H5  +  I)— CH3        > 

! 

(Na) 

Sodium  aceto^icetate,  ester 

CH3— CO— CH— COOC2H5 
CH3 

Ethyl  ester  of  methyl  aceto 

acetic  acid 
17 


258  ORGANIC  CHEMISTRY 

Such  an  alkyl  derivative  may  then  yield  a  new  sodium  salt  and  the 
sodium  again  be  replaced  by  an  alkyl  radical  and  a  di-alkyl  derivative 
may  be  obtained. 

+  NaOC2H5 
CH3— CO— CH— COOC2H5 » 

I 
CH3 

Ethyl  ester  of  methyl  aceto 
acetic  acid 

Na  CH3 

I                         + 1— CH3  I 

CH3— CO— C— COOC2H5 CH3— CO— C— COOC2H5 

CH3  CH3 

Sodium  salt  Ethyl  ester  of  di-methyl  aceto 

acetic  acid 

As  the  alkyl  radical  may  be  varied  at  will  it  becomes  possible  to  intro- 
duce into  the  carbon  group  linked  between  the  two  carbonyl  groups 
any  one  or  any  two  radicals.  Also  the  sodium  salt  reacts  with  acyl 
halides  by  which  it  becomes  possible  to  introduce  not  only  alkyl  but 
also  acyl  radicals. 

Aceto  Acetic  Ester  Syntheses. — These  alkyl  and  acyl  derivatives 
of  ethyl  aceto  acetate,  both  the  mono-  and  the  di-  derivatives,  react 
now  on  hydrolysis  in  the  two  ways  given  above,  i.e.,  by  the  ketone  hydro- 
lysis or  the  acid  hydrolysis  and  we  may  thus  obtain  a  large  number  of 
ketones  and  acids  as  desired. 

Ketone  hydrolysis 
CH3  CH3 

I                        +H— OH  i 

CH3— CO— C— COOC2H5        »       CH3— CO— CH  +  C2H5— OH 


CH3  CH3 

Di-methyl  aceto  acetic  ester  Methyl  iso-propyl  ketone 

R  R 

I  +H— OH                        I  * 

CH3— CO— C— COOC2H5 CH3— CO— CH  +  C2H6— OH 

I  ~C°2                           I 

R  R 

Di-alkyl^derivative  Ketone 


1 


ALDEHYDE  ACIDS   AND   KETONE   ACIDS  259 

Acid  hydrolysis 


CH 


+  2H—  OH 
CH3—  CO—  C—  COOC2H5       --  -        CH3—  COOH  + 

Acetic  acid 


CH3 

Di-methyl  aceto  acetic  ester 

CH3 

CH—  COOH  +  C2H6—  OH 

I 
CH3 

Iso-butyric  acid 

R 

I  +  2H—  OH 

CH3—  CO—  C—  COOC2H5       --  > 
|  +H20 

R 

Di-alkyl  derivative 

R 
CH3—  COOH  +  CH—  COOH  +  C2H5—  OH 

! 

R 

Acids 

We  thus  see  what  a  variety  of  ketones  and  acids  are  possible  of 
synthesis  by  means  of  ethyl  aceto  acetate  as  not  only  the  open  chain 
compounds  which  we  are  studying  but  cyclic  compounds  and  those 
containing  nitrogen  may  result.  Some  of  the  important  ones,  e.g., 
anti-pyrine  will  be  mentioned  later  (Part  II). 

Action  of  Hydrogen  and  of  Ammonia.  —  Another  reaction  of  aceto 
acetic  ester  should  be  mentioned.  When  hydrogen  (sodium  amalgam), 
ammonia  or  alkyl  primary  amines  react  with  aceto  acetic  ester,  crotonic 
acid  (p.  173)  CH3—  CH=  CH—  COOH,  or  derivatives  of  it  are  obtained. 
The  fact  that  crotonic  acid  contains  a  double  bond  seems  to  indicate 
the  presence  of  a  double  bond  in  aceto  acetic  ester,  and  would  be  evi- 
dence for  the  enol  form. 

-H—  OH 
CH3—  C(OH)  =  CH—  COOC2H5  +  H—  NH2        --  > 

Aceto  acetic  acid  ester 

CH3—  C(NH2)  =  CH—  COOC2H5 

Amino  crotonic  acid  ester 


260  ORGANIC  CHEMISTRY 

However,  the  reaction  may  be  written  also  with  the  keto  form  as  follows, 
in  the  case  of  the  action  of  hydrogen. 

CH3— CO—  CH2— COOC2H5  +  H2         > 

Aceto  acetic  acid  ester 

-H— OH 
CH3— CH(OH)— CH2— COOC2H5 

Hydroxy  butyric  acid 

CH3— CH  =  CH— COOC2H5 

Crotonic  acid  ester 

Intermediate  addition  products  are  formed  in  both  cases  and  in  the 
last  reaction  the  compound  has  been  definitely  proven  to  be  /3-hydroxy 
butyric  acid. 

Levulinic  Acid       CH3— CO— CH2— CH2— COOH 

We  need  simply  mention  briefly  the  simplest  representative  of  the 
gamma-ketone  acids.  Levulinic  acid  derives  its  name  from  the  fact  that 
it  is  formed  by  the  decomposition,  with  boiling  dilute  acids,  of  fructose 
sugar  which  is  also  known  as  levulose.  It  is  in  fact  a  characteristic 
product  of  similar  decompositions  of  hexose  sugars  or  higher  carbo- 
hydrates which  yield  hexoses.  The  constitution  as  a  ketone  acid  as 
given  above  has  been  established.  It  may  also  be  termed  aceto  pro- 
pionic  acid  and  is  isomeric  with  methyl  aceto  acetic  acid  (p.  257).  It 
is  a  crystalline  solid,  soluble  in  water,  melting  at  33.5°  and  boiling  at 
250°.  We  shall  refer  to  this  compound  later  in  connection  with  the 
synthesis  of  rubber. 


IX.   POLY-ALDEHYDES,   POLY-KETONES  AND   POLY-CAR- 
BOXY  ACIDS 

A.  DI-ALDEHYDES  AND  DI-KETONES 

We  have  considered  poly-hydroxy  alcohols  and  then  mixed  com- 
pounds such  as  halogen  alcohols,  halogen  aldehydes,  halogen  acids, 
hydroxy  acids,  aldehyde  acids  and  ketone  acids.  We  have  also 
mentioned  but  deferred  the  discussion  of  aldehyde  alcohols  and  ketone 
alcohols  and  also  of  amino  acids.  Our  next  large  group  will  be  the 
poly-carboxy  acids  but  before  we  consider  them  we  should  take  up  the 
two  intermediate  classes  of  di- or  poly- compounds,  viz.,  those  containing 
two  aldehyde  or  two  ketone  groups,  i.e.,  the  di-aldehydes  and  di-ketones. 
There  is  also  one  more  group  of  mixed  compounds,  viz.,  the  aldehyde 
ketone  compounds  but  these  also  in  so  far  as  they  need  to  be  considered 
will  come  in  later  in  connection  with  the  carbohydrates. 

I.  DI-ALDEHYDES 
Glyoxal       CHO— CHO 

The  simplest  di-aldehyde  possible  is  the  one  obtained  by  oxidizing 
ethyl  alcohol  or  acetic  aldehyde  with  nitric  acid. 

CH2— OH    _|_o    CHO    +o    CHO 
CH3  CH3          CHO 

Ethyl  alcohol  Acet-aldehyde  Glyoxal 

Di-aldehyde 

The  di-aldehyde  compound  is  known  as  glyoxal.  It  is  obtained  as  a 
colorless,  amorphous  solid  readily  soluble  in  water.  In  all  its  reactions 
it  possesses  the  properties  of  an  aldehyde  and  its  constitution  and  re- 
lationship are  as  represented  above. 

II.  Dl-KETONES 

The  di-ketones  are  similar  to  the  ketone  acids  in  being  classified 
according  to  the  relative  position  of  the  two  carbonyl  groups.  We 
have,  therefore,  alpha-,  beta-,  gamma-,  etc.,  di-ketones  as  follows. 

R— CO— CO— R  a-Di-ketones  or  i-2-Di-ketones 

R— CO— CH2— CO— R  0-Di-ketones  or  i-3-Di-ketones 

R — CO — CH2 — CH2 — CO — R  7-Di-ketones  or  i-4-Di-ke tones 

261 


262  ORGANIC  CHEMISTRY 

i-2-DI-KETONES    Di-acetyl    CH3— CO— CO— CH3. 

From  Aceto  Acetic  Ester. — The  simplest  di-ketone,  which  is  natu- 
rally an  a/^a-di-ketone,  is  CH3-CO— CO— CH3,  di-acetyl.  It  is 
made  from  methyl  aceto  acetic  ester  by  an  interesting  reaction  involving 
the  ketone  hydrolysis.  When  aceto  acetic  ester  is  treated  in  the  hot 
with  dilute  alkali  the  ketone  hydrolysis  takes  place.  If,  however,  the 
treatment  is  in  the  cold,  hydrolysis  results  simply  in  the  formation  of 
the  potassium  salt. 

+  KOH 
CH3— CO— CH— COOC2H5 > 

CH3 

Methyl  aceto  acetic  ester 

CH3— CO— CH— COOK    +    C2H5OH 
CH3 

Potassium  salt  of 
methyl  aceto  acetic  acid 

When  this  salt  is  treated  with  nascent  nitrous  acid,  HO — NO,  the 
compound  is  first  converted  into  the  free  acid  which  loses  carbon  dioxide 
forming  a  ketone.  This  ketone  then  reacts  with  the  nitrous  acid  and 
the  oximino  group,  (  =  N — OH),  becomes  linked  to  the  carbon  atom 
which  was  originally  linked  between  the  two  carbonyl  groups. 

+  acid                                                   —  CO2 
CH3— CO— CH— COOK »     CH3— CO— CH— (COO)H » 

!  I 

CH3  CH3 

Potassium  salt  of  methyl  Methyl  aceto  acetic  acid 

aceto  acetic  acid 

CH3— CO— CH2 
CH3 

Methyl  ethyl  ketone 

CH3— CO— C(H2    +    O)N— OH    >    CH3— CO— C  =  N— OH 

I  I 

CH3  CH3 

Methyl  ethyl  Iso-nitroso  derivative 

ketone 


POLY-ALDEHYDES  AND  POLY-KETONES  263 

Iso-nitroso  and  Oxime  Compounds. — This  iso-nitroso  derivative  of 
the  mono-ketone  (methyl  ethyl  ketone)  is  also  an  oxime  of  the  di-ketone 
(di-acetyl)  as  may  be  shown  by  the  following  relationships. 

CH3  CH3 

(rearrange- 
CH3— CO— CH(H  +HO)—  NO >  CH3— CO— CH— NO 

Methyl  ethyl  Nitroso  methyl  ment) 

ketone  ethyl  ketone 

CH3  CH3 

|  +  H20  | 

CH3— CO— C  =  N— OH         ~1^         CH3— CO— C(O  +  H2)N— OH 

Iso-nitroso  TT  r\  Di-acetyl  Hydroxyl 

methyl  ethyl  ketone  n.2vJ  amine 

Oxime  of  di-acetyl 

This  rearrangement  of  nitroso  derivatives  into  iso-nitroso  derivatives 
or  oximes  is  of  especial  importance  in  connection  with  the  benzene 
compounds  and  a  group  of  nitroso  dyes.  The  oxime  yields  the  di- 
ketone  when  hydrolyzed  by  boiling  with  dilute  sulphuric  acid,  as  above. 
Di-acetyl,  being  a  di-ketone,  reacts  in  all  respects  as  a  di-carbonyl  com- 
pound especially  in  yielding  both  the  mono-oxime  as  above  and  also  a 
di-oxime. 

i-3-DI-KETONES    Acetyl  Acetone    CH-j— CO— CH2— CO— CH3 

The  foto-di-ketones  are  very  similar  to  the  fo/a-ketone  acids  both 
in  their  formation  and  reactions. 

From  Ethyl  Acetate. — The  simplest  member  of  this  group  is  CH3 — 
CO — CH2 — CO — CH3  which  is  plainly  acetyl  acetone.  It  is  best  made 
by  a  reaction  exactly  analogous  to  the  one  used  in  preparing  aceto 
acetic  ester.  In  making  the  latter  ethyl  acetate  is  condensed  with  itself 
by  means  of  sodium  and  ethyl  alcohol  (sodium  ethylate)  as  described 
already  (p.  254).  If  instead  of  condensing  with  another  molecule  of 
itself  ethyl  acetate  condenses  with  acetone  we  obtain  acetyl  acetone, 
as  follows : 

CH3— CO(OC2H5  +  H)CH2— CO— CH3    > 

Ethyl  acetate  Acetone 

CH3— CO— CH2— CO— CH3 

Acetyl  acetone 

By  using  any  other  methyl  alkyl  mono-ketone  other  fo/a-di-ketones 
may  be  obtained. 


264  ORGANIC  CHEMISTRY 

In  these  foto-di-ketones  we  have  the  same  condition  of  the  linkage 
of  a  methylene  group,  (  — CH2 — ),  between  two  carbonyl  groups  as  we  had 
in  the  case  of  aceto  acetic  acid.  The  hydrogen  atoms  of  this  methylene 
group  like  the  similar  ones  in  aceto  acetic  ester  are  replaceable  by 
metals,  (sodium),  and  through  these  sodium  compounds  new  alkyl  or 
acyl  radicals  may  be  introduced.  By  boiling  with  alkalies  the  bela- 
di-ketones  undergo  a  mixed  acid  and  ketone  hydrolysis  and  there  is 
obtained  both  an  acid  and  ketone. 

HO|-H                          (alkali) 
CH3— CO|— CH2— CO— CH3 > 

0-Di-ketone  +  Water 

CH3— COOK  +  CH3— CO— CH3 

Acid  (salt)  Ketone 

B.  POLY-CARBOXY  ACIDS 
I.  SATURATED  DI-BASIC  ACIDS 

Corresponding  to  the  poly-hydroxy  or  poly-acid  alcohols  are  the 
poly-carboxy  or  poly-basic  acids.  The  simplest  of  these  poly-basic 
acids  are  those  containing  two  carboxyl  groups.  Such  compounds 
contain  two  acid  hydrogens  and  are  thus  di-basic,  exactly  analogous 
to  the  di-basic  inorganic  acids,  e.g.,  sulphuric  acid,  HO — S02 — OH. 

Oxalic  Acid      HOOC— COOH 

Synthesis  from  Cyanogen. — The  simplest  di-basic  acid  known  is 
the  common  substance  oxalic  acid.  Its  composition  corresponds  to 
the  formula  H2C2O4.  The  compound  is  definitely  di-basic  so  that  it 
must  contain  two  acid  hydrogens,  i.e.,  two  carboxyl  groups.  As  two 
carboxyl  groups  alone  correspond  to  the  formula  given  this  would 
indicate  that  the  constitution  must  be  that  of  two  carboxyl  groups 
linked  together,  i.e.,  HOOC— COOH.  This  constitution  is  also  proven 
by  its  synthesis  from  cyanogen.  Cyanogen  has  previously  been  men- 
tioned as  an  example  of  a  radical  which  exists  as  such.  It  is  prepared 
from  mercuric  cyanide  by  heating,  the  reaction  being  exactly  analogous 
to  that  of  the  formation  of  oxygen  from  mercuric  oxide  by  heat.  Cy- 
anogen is  thus  analogous  to  molecular  oxygen  and  is  represented  as 
(NC — CN).  The  two  reactions  may  be  represented  as  follows: 
2HgO  -f  heat  — >  2Hg  +  O2  or  O  =  O 

Mercuric  oxide  Molecular  oxygen 

Hg(CN)2  +  heat      — >    Hg  +   (CN)2    or    N  =  C— C  =  N 

Mercuric  cyanide  Molecular  cyanogen 


DI-BASIC   ACIDS  265 

Hydrolysis  of  Cyanogen.  —  Organic  compounds  containing  this 
cyanogen  group,  (  —  CN),  yield  acids  on  hydrolysis,  hence  they  are 
called  acid  nitriles  (p.  69).  In  this  hydrolysis  the  cyanogen  group, 
(  —  CN),  is  converted  into  the  carboxyl  group,  (  —  COOH),  and  am- 
monia, NH3  (p.  68).  The  hydrolysis  of  cyanogen  gas  would  there- 
fore yield  di-carboxyl,  as  follows: 

CN  +  2H2O  COOH    +    NH3  COONH4 


2H20  COOH    +    NH3  COONH4 

Cyanogen  Oxalic  acid  Ammonium  oxalate 

(Di-carboxyl) 

As  oxalic  acid  is  the  product  obtained  by  this  hydrolysis  it  must 
have  the  constitution  as  represented,  i.e.,  it  is  di-carboxyl.  In  fact, 
when  cyanogen  is  hydrolyzed  ammonium  oxalate  is  obtained  which, 
of  course,  results  from  the  combination  of  the  oxalic  acid  and  ammonia 
as  first  formed. 

From  Glycol.  —  A  second  synthesis  which  proves  the  constitution 
of  oxalic  acid  is  that  from  ethylene  glycol,  HO—  CH2—  CH2—  OH.  On 
the  complete  oxidation  of  glycol  with  nitric  acid  oxalic  acid  is  obtained. 
This  is  plainly  the  oxidation  of  each  of  the  primary  alcohol  groups  to 
carboxyl,  and  may  be  represented  as  follows, 

CH2—  OH  COOH 

|  +         2O2          —  >         |  +       2H2O 

CH2—  OH  COOH 

Ethylene  glycol  Oxalic  acid 

From  Hexa-chlor  Ethane.  —  It  may  also  be  prepared  by  oxidizing  a 
derivative  of  ethane,  viz.,  hexa-chlor  ethane,  CCle,  with  potassium 
hydroxide.  This  reaction  may  be  considered  as  yielding  the  complete 
oxidation  product  of  ethane  by  the  replacement  of  the  six  chlorine  atoms 
by  six  hydroxyl  groups.  This  then  loses  water,  as  in  the  case  of  all 
compounds  which  contain  more  than  one  hydroxyl  group  linked  to 
one  carbon  atom,  and  di-carboxyl,  or  oxalic  acid  results,  as  follows, 
Cl  (OH) 

Cl—  C—  Cl  +  3K—  OH  (H)0—  C—  OH  _2H2O  O  =  C—  OH 

Cl—  C—  Cl  +  3K—  OH  (H)O—  C—  OH  O  =  C—  OH 

I  Oxalic  acid 

Cl  (OH) 

Hexa-chlor 
ethane 


266 


ORGANIC  CHEMISTRY 


Oxidation  Products  of  Ethane — Oxalic  acid  is  thus  the  simplest  di- 
carboxy  acid  possible.  It  may  be  considered  as  derived  from  ethane 
by  the  oxidation  of  both  methyl  groups  to  primary  alcohol,  aldehyde, 
and  carboxyl  groups  successively.  The  entire  series  of  oxidation 
relationships,  including  all  of  the  intermediate  compounds  which  we 
have  already  discussed,  may  be  represented  as  follows: 


CH3 


CH2OH 


CH2OH 


CH3 

Ethane 


CH3 

Ethyl  alcohol 


CHO 


CH2OH 

Glycol 


I        I 


CHO 


CHO 


CH3 

Acetic  aldehyde 


COOH 


CH3 

Acetic  acid 


CH2OH 

Glycolic  aldehyde 


COOH 


CH2OH 

Glycolic  acid 


CHO 

Glyoxal 

I 

COOH 


CHO 

Glyoxylic  acid 


COOH 


COOH 

Oxalic  acid 


As  each  poly-hydroxy  alcohol  must  have  as  many  carbon  groups  as 
it  has  hydroxyls,  so  also,  a  poly-basic  acid  must  have  at  least  as  many 
carbon  groups  as  it  has  carboxyls  and  the  simplest  di-basic  acid  must 
be  derived  from  the  two  carbon  hydrocarbon. 

Relation  to  Formic  Acid. — The  relation  of  oxalic  acid  to  formic 
acid  is  shown  by  a  series  of  important  reactions.  It  will  be  recalled, 
(p.  134),  that  formic  acid  may  be  made  by  rapidly  heating  oxalic  acid, 
or  by  heating  oxalic  acid  in  glycerol.  The  reaction  taking  place  is, 
in  effect,  simply  the  loss  of  carbon  di-oxide,  as  follows, 


H(OOC)— COOH 

Oxalic  acid 


H— COOH 

Formic  acid 


C02 


With  glycerol  the  reaction  takes  place  more  easily  and  at  a  lower  tem- 
perature, thus  preventing  the  further  breaking  down  of  the  formic  acid. 
This  is  due  to  the  intermediate  formation  of  an  ester  of  glycerol  and 
formic  acid.  This  ester  is  then  hydrolyzed  by  the  action  of  the  water, 


DI-BASIC   ACIDS  267 

which  is  present  as  water  of  crystallization  of  the  hydrous  oxalic  acid, 
and  the  formic  acid  is  set  free. 

CH2— (OH  +  H)OOC— H            CH2— (OOC— H  +  H)— OH 
CH  —OH  >  CH  —OH  > 

I  Formic  I 

acid 

CH2— OH  CH2— OH 

Glycerol  Glyceryl 

formate 

CH2— OH 

I       • 
CH— OH    +    H— COOH 

Formic  acid 

CH2— OH 

Glycerol 

In  this  way  the  glycerol  acts  as  a  carrier  of  the  formic  acid  and  is  used 
over  and  over  just  as  is  the  case  with  the  sulphuric  acid  in  the  prepara- 
tion of  ether.  As  formic  acid  breaks  down  by  heating,  and  yields  car- 
bon monoxide  and  water,  and  oxalic  acid,  by  similar  treatment  yields 
formic  acid  and  carbon  dioxide  we  may  represent  the  complete  breaking 
down  of  oxalic  acid  as  follows, 

COOH  H 

|       — »  C02  +   |       — >  CO  +  H2O 

COOH  COOH 

Oxalic  acid  Formic  acid 

Therefore  the  final  products  of  the  decomposition  of  oxalic  acid  by  heat 
are,  carbon  di-oxide,  carbon  mon-oxide  and  water.  It  will  be  recalled 
that,  in  elementary  chemistry,  the  method  of  preparing  carbon  mon- 
oxide is  by  heating  oxalic  acid  with  sulphuric  acid.  The  gaseous  prod- 
ucts are  passed  through  a  solution  of  potassium  hydroxide  to  absorb 
the  carbon  di-oxide,  and  the  resulting  gas  is  pure  carbon  mon-oxide. 
Reduction  of  Carbon  Di-oxide. — This  whole  series  of  reactions 
shows  us  the  relation  that  exists  between  carbon  and  its  oxidation  prod- 
ucts, carbon  monoxide  CO,  and  carbon  dioxide,  CO2.  It  has  already 
been  shown,  that  a  general  method  for  the  preparation  of  mono-basic 
acids  is  by  the  action  of  carbon  di-oxide  upon  the  metallic  alkyl  com- 
pounds, as  follows, 

R— Na    +    CO2     >     R— COOH 

Sodium  alkyl  Mono  basic  acid 


268  ORGANIC  CHEMISTRY 

If  hydrogen  alone  is  used  the  product  is  formic  acid, 
H— H      +      CO2    >    H— COOH 

Formic  acid 

Now,  sodium  oxalate  may  be  prepared  by  the  action  of  carbon  di-oxide 
upon  sodium,  at  360°, 

Na— Na    +     2CO2    >    NaOOC— COONa 

Sodium  oxalate 

In  this  last  reaction,  it  will  be  observed,  twice  as  much  carbon  di-oxide 
is  used  as  in  the  preceding  reaction  in  the  formation  of  formic  acid 
from  carbon  di-oxide.     Now,  carbon  mon-oxide  and  carbon  are  the 
reduction  products  of  carbon  di-oxide,  and  in  the  light  of  all  of  the 
reactions  which  we  have  just  considered,  we  may  represent  the  theo- 
retical stages  in  the  reduction  of  carbon  di-oxide,  as  follows, 
2CO2  +    H2       — *    HOOC— COOH  Oxalic  acid 
2CO2  +  2H2       — >     2H— COOH        Formic  acid 
2CO2  -f  4H2       -?     2C  -f  4H2O         Carbon  +  water 
2CO2  H-  8H2     — >     2CH4  +  4H2O  Methane  -f  water 
Or,  as  follows, 
C02  +H2  COOH  heat  C02     +H2         H-COOH 

'  +  \-  +H2 

CO2  COOH  H— COOH  -  — »  H2O  +  CO 

Carbon  Oxalic  Formic  acid  heat  Car- 

di-oxide  acid  bon 

mon- 
oxide 

+  2H2 

H20     +     C     + >    CH4 

Carbon  Methane 

(Hydrocarbon) 

Thus,  carbon  monoxide,  oxalic  acid  and  formic  acid  are  intermediate 
products  in  the  reduction  of  carbon  di-oxide  to  elemental  carbon.  If  the 
reduction  is  continued  beyond  the  stage  of  free  carbon  we  shall  obtain 
the  hydrocarbons  which  stand  at  the  other  extreme  to  carbon  di-oxide, 
in  respect  to  the  element  carbon.  The  hydrocarbons  are  thus  the  re- 
duction product  and  carbon  dioxide  the  oxidation  product  of  carbon. 
In  other  words  the  final  reduction  products  of  carbon  dioxide  are  hydro- 
carbons and  vice-versa  the  final  oxidation  product  of  hydrocarbon^  is 
carbon  dioxide. 

(CO,  H— COOH,  HOOC— COOH) 

CH4    «—  C  — >     CO2 

c?rybdons    Reduction  Carbon  Oxidation 


DI-BASIC   ACIDS  269 

This  relationship  is  illustrated  by  the  fact,  that  both  formic  acid 
and  oxalic  acid  are  obtained  by  the  oxidation  of  many  organic  substances, 
e.g.,  wood,  starch,  sugar  and  alcohols,  which  are  themselves,  as  has  been 
explained  in  the  case  of  alcohol,  oxidation  products  of  the  hydrocarbons. 
Thus  oxalic  acid  and  formic  acid  stand  close  to  carbon  di-oxide,  the 
final  oxidation  product  of  carbon,  while  the  alcohols,  sugar,  starch 
and  similar  oxygen-containing  organic  substances,  stand  farther  away 
from  carbon  di-oxide  and  closer  to  the  hydro-carbons  of  which  they  are 
oxidation  products.  This  whole  oxidation  and  reduction  relationship 
of  the  element  carbon  is  involved  in  the  complicated  bio-chemical  reactions 
that  occur  in  living  plants  and  animals.  It  will  be  somewhat  clearer 
when  we  have  studied  the  proteins  and  carbohydrates  but  the  study  of 
the  function  and  properties  of  living  cells  and  the  associated  catalytic 
action  of  enzymes  is  necessary  for  anything  like  a  full  understanding. 

Commercial  Preparation. — The  commercial  method  for  preparing 
oxalic  acid,  up  to  a  few  years  ago,  was  by  the  oxidation  of  sawdust 
or  sugar.  In  practice  sawdust  was  oxidized  by  heating  it  with  fused 
alkali  by  which  process  the  alkali  salt  of  oxalic  acid  was  obtained. 
When  sugar,  or  similar  organic  substances,  like  cellulose,  are  oxidized 
the  reaction  may  be  illustrated  by  the  oxidation  of  the  hexa-hydroxy 
hexane,  or  mannitol,  as  follows : 

CH2OH—  (CHOH)4—  CH2OH+0 >  COOH—  COOH+CO2+H2O 

Mannitol  Oxalic  acid 

The  two  primary  alcohol  groups,  viz.,  the  two  end  carbon  groups, 
become  oxidized  to  carboxyl.  The  intermediate  secondary  alcohol 
groups  become  completely  oxidized  to  carbon  di-oxide  and  water  and  are 
thus  destroyed  so  that  the  two  end  groups  yielding  the  two  carboxyls 
become  directly  linked  as  oxalic  acid.  As  the  end  carbon  groups  are 
the  only  ones  capable  of  existence  as  primary  alcohol  groups  and  there- 
fore able  to  yield  carboxyl  on  oxidation,  the  reaction  as  above  written 
is  in  accordance  with  both  the  facts  and  the  possibilities. 

Goldschmidt  Process. — While  this  oxidation  of  organic  substances 
was  formerly  the  commercial  method  of  preparing  oxalic  acid  it  has 
now  been  replaced  by  another  process  known  as  the  Goldschmidt 
Process.  This  process  rests  upon  the  reaction,  previously  described, 
(p.  267),  by  which  oxalic  acid  decomposes  into  formic  acid  and  carbon 
di-oxide.  When,  however,  formic  acid,  or  better  one  of  its  salts,  is 


270  ORGANIC  CHEMISTRY 

heated  to  400°  hydrogen  is  split  off  and  practically  the  reverse  of  the 
above  reaction  occurs  with  the  formation  of  oxalic  acid  as  follows: 

heat 
NaOOC— (H    +    H)— COONa »    NaOOC— COONa    +    H2 

Sodium  formate  Sodium  oxalate 

In  the  process  as  commercially  carried  out,  the  formic  acid  is  first 
prepared  from  carbon  mon-oxide  and  sodium  hydroxide  (p.  134). 

HO— Na     +      CO        >        H— COONa 

Sodium  Formic  acid 

hydroxide  (Salt) 

This  is  accomplished  by  adding  sodium  hydroxide  to  heated  coke 
and  then  passing  over  it  a  current  of  hot  carbon  mon-oxide.  Also, 
instead  of  decomposing  the  formate  at  400°  it  may  be  decomposed  in 
the  same  way  by  heating  to  a  lower  temperature  in  sulphuric  or  phos- 
phoric acid.  Thus  the  simplest  acids,  in  both  the  mono-basic  and  the 
di-basic  series  are  each  made  from  carbon  mon-oxide  and  an  alkali 
involving  the  reactions  that  have  just  been  discussed  and  which  show 
the  relation  which  exists  between  the  oxides  of  carbon  and  the  two 
acids  formic  and  oxalic. 

Properties  of  Oxalic  Acid. — Oxalic  acid  has  been  known  from  early 
times  as  the  acid  potassium  and  acid  calcium  salts  in  which  form  it  is 
present  in  sorrel,  or  oxalis,  and  in  other  plants,  especially  rhubarb. 
In  some  cases,  as  in  Calladium  and  in  the  Jack  in  the  Pulpit,  the  cal- 
cium salt  is  present  in  crystalline  form  and  gives  to  the  plant  a  sharp 
prickly  taste.  Oxalic  acid  crystallizes  from  water  in  beautiful  color- 
less mono-clinic  prisms  which  are  often  of  considerable  length.  The 
crystals  contain  two  molecules  of  water  of  crystallization  which  are 
lost  at  105°.  The  anhydrous  acid  melts  at  189°  and  can  be  partially 
sublimed  without  decomposition.  Its  decomposition  by  heat,  into 
formic  acid  has  already  been  discussed.  It  is  soluble  in  about  12  parts 
of  water.  It  is  a  poison,  and  it  has  been  claimed  that  its  poisonous 
action  is  due  to  its  breaking  down  and  yielding  carbon  mon-oxide. 
With  nitric  acid  oxalic  acid  is  slowly  oxidized  to  carbon  di-oxide  but 
with  potassium  permanganate,  in  acid  solutions,  it  is  very  easily 
oxidized.  This  last  reaction  is  the  basis  of  the  use  of  oxalic  acid  and  its 
salts  in  volumetric  analysis.  The  salts  of  oxalic  acid  are  used  as 
mordants  in  dyeing.  The  iron  salts,  because  of  their  strong  reducing 
properties,  are  used  as  photographic  developers. 


DI-BASIC  ACIDS 


271 


Derivatives  of  Oxalic  Acid 

Salts. — Oxalic  acid  forms  two  series  of  salts,  due  to  its  di-basic 
character,  i.e.,  the  presence  of  two  carboxyl  groups.  These  are  the 
acid  sails  and  the  neutral  salts. 

Acid  Potassium  Oxalate,  KOOC— COOH.— This  salt  is  the  form 
in  which  oxalic  acid  occurs  in  sorrel.  When  obtained  from  this  source, 
however,  the  acid  salt  combines  with  a  molecule  of  free  acid  forming 
crystals  with  two  molecules  of  water,  viz. 

Potassium  Tetroxalate,  KOOC— COOH  •  HOOC— COOH  •  2H2O  — 
This  salt  is  also  known  commercially  as  salt  of  sorrel.  The  salts  of 
oxalic  acid  with  the  alkali  metals  are  more  soluble  in  water  than  the 
free  acid  itself.  Both  the  salts  and  the  free  acid  dissolve  iron  rust  and 
iron  inks  and  are  often  used  for  the  purpose  of  removing  such  substances 
from  cloth. 

Esters,  Acid  Chlorides,  Acid  Amides. — Just  as  oxalic  acid,  because 
of  its  di-basic  character,  forms  two  series  of  salts,  it  also  forms  two 
series  of  the  other  acid  derivatives,  viz.,  esters,  acid  chlorides  and  acid 
amides. 


COOH 


COOC2H5 


COOC2H5 


COOH 

Oxalic  acid 

COOH 


COOH 

Ethyl  oxalic  acid 

CO— Cl 


COOC2H5 

Di-ethyl  oxalate 

CO— Cl 


COOH 

Oxalic  acid 

COOH 


COOH 

Oxalic  acid 


COOH 

Oxalic  acid  chloride 

CO— NH2 


COOH 

Oxamic  acid 


CO— Cl 

Oxalyl  chloride 

CO— NH2 


CO— NH; 

Oxamide 


The  di-ethyl  ester  of  oxalic  acid  is  easily  prepared  by  heating  anhy- 
drous oxalic  acid  with  absolute  alcohol, 


HOOC— COOH  +  2C2H5OH 

Oxalic  acid  Ethyl  alcohol 


C2H5OOC— COOC2H5  +  2H20 

Di-ethyl  oxalate 


Di-ethyl  oxalate  is  a  liquid  with  a  characteristic  odor  and  which 
boils  at  1 86°.  Ethyl  oxalic  acid,  HOOC— COOC2H5,  is  a  liquid  which 
boils  at  117°,  under  15  mm.  pressure. 


272  ORGANIC  CHEMISTRY 

The  acid  chlorides  of  oxalic  acid  can  not  be  prepared  by  the  direct 
action  of  phosphorus  penta-chloride  on  the  acid  but  by  its  action  upon 
the  esters, 

HOOC— COOC2H5+PC15  >  HOOC— CO— C1+C2H5— C1+POC13 

Ethyl  oxalic  acid  Oxalic  acid  chloride 

C2H5OOC— COOC2H5  +  2PC15        > 

Di-ethyl  oxalate  C1_QC— CO— Cl  +   2C2H5— Cl   +    2POC13 

Oxalyl  chloride 

The  amides  of  oxalic  acid  are  also  best  prepared  by  the  action  of 
ammonia  not  upon  the  acid  itself  or  the  acid  chloride  but  upon  the 
esters. 

HOOC— CO(OC2H5  +  H)NH2  >  HOOC— CO— NH2  +  C2Hf)OH 

Ethyl  oxalic  acid  Oxamic  acid 

C2H50)OC— CO(OC2H5  +  2H)NH2        > 

Di-ethyl  oxalate  H2N— OC— CO— NH2  +  2C2H5— OH 

Oxamide 

The  preparation  of  oxamide  is  easily  accomplished  in  the  laboratory. 
On  heating  anhydrous  oxalic  acid  with  absolute  alcohol  and  then  dis- 
tilling di-ethyl  oxalate  is  obtained.  On  adding  concentrated  ammonium 
hydroxide  to  this  the  oxamide  is  thrown  down  at  once  as  an  abundant 
white  precipitate. 

Another  reaction  by  which  both  oxamic  acid  and  oxamide  may  be 
prepared  is  by  heating  the  ammonium  salt  of  oxalic  acid.  The  reaction 
takes  place  in  two  steps.  First,  by  the  loss  of  one  molecule  of  water,  the 
ammonium  salt  of  oxamic  acid  is  formed.  Second,  by  the  loss  of  another 
molecule  of  water,  this  is  converted  into  oxamide,  as  follows: 

COONH4         _H20      CO— NH2    _H2o       CO— NH2 
COONH4  COONH4  CO— NH2 

Ammonium  oxalate  Ammonium  oxamate  Oxamide 

The  final  products  obtained  on  heating  ammonium  oxalate  are 
CO2,  CO,  NH3,  (CN)2,  HCN,  and  oxamide. 

This  relation  between  the  ammonium  salt  of  an  acid  and  the  amide 
of  the  acid  has  been  previously  discussed  (p.  145).  The  amides  of 


DI-BASIC   ACIDS  273 

oxalic  acid  yield  methyl  substitution  products  in  which  the  substitution 
is  in  the  amino  group. 

CO— NH2  CO— N(CH3)2        CO— NH2  CO— NH(CH3) 

COOH  COOH  CO— NH2  CO— NH(CH3) 

Oxamic  acid  Di-methyl  oxamic  acid  Oxamide  Di-methyl  oxamide 

Oxalic  acid  does  not  form  an  anhydride  which  is  undoubtedly  due  to 
the  space  relations  of  the  two  hydroxyl  groups. 

Malonic  Acid     HOOC— CH2— COOH,    Propan-di-oic  Acid 
Relation  to  Propane. — As  oxalic  acid,  the  simplest  di-basic  acid  is 
derived  from  ethane  the  next  higher  member  of  the  series  should  be 
derived  from  propane,  C3H8. 

CH3— CH2— CH3        »        CH2OH— CH2— CH2OH        > 

Propane  i-3-Propan-di-ol 

HOOC— CH2— COOH 

Malonic  acid 
Propan-di-oic  acid 

This  acid  is  known  as  malonic  acid  and  its  systematic  name,  indicat- 
ing its  relation  to  propane,  is  propan-di-oic  acid.  As  it  may  also  be 
derived  from  methane  by  the  substitution  of  two  carboxyl  groups,  it 
is  also  known  as  methane  di-carboxylic  acid.  It  may  similarly  be 
regarded  as  a  mono-carboxyl  substituted  acetic  acid. 

Relation  to  Methane  and  Acetic  Acid. — The  two  syntheses  of  mal- 
onic acid  which  prove  its  constitution  also  show  its  relation  to  methane 
and  to  acetic  acid  as  indicated  above.  Di-cyano  methane,  which  is 
made  from  di-chlor  methane  by  the  action  of  potassium  cyanide,  yields 
malonic  acid  on  hydrolysis  and  on  that  account  is  also  known  as 
malonic  nitrile. 

Cl)— CH2—  (Cl  +  2K)— CN    >    NC— CH2— CN  +  4H2O     > 

Di-chlor  methane  Malonic  nitrile 

Di-cyano  methane 

HOOC— CH2— COOH  +  2NH3 

Malonic  acid 
Di-carboxy  methane 

In  a  similar  way  mono-chlor  acetic  acid  (p.  234)  by  means  of 
potassium  cyanide  yields  mono-cyanogen  acetic  acid  and  this  on 
hydrolysis  yields  malonic  acid,  as  follows: 

CH3— COOH        >        Cl— CH2— COOH        > 

Acetic  acid  Mono-chlor  acetic  acid 

NC— CH2— COOH  — >        HOOC— CH2— COOH 

Mono-cyano  acetic  acid  Malonic  acid 

18 


274  ORGANIC  CHEMISTRY 

In  a  reverse  way  both  acetic  acid  and  methane  may  be  obtained 
when  malonic  acid  is  heated  just  above  its  melting  point,  140°-! 50°. 
It  loses  one  molecule  of  carbon  dioxide  and  yields  acetic  acid  which 
then  by  loss  of  a  second  molecule  of  carbon  dioxide  yields  methane. 

-CO2                                  -CO2 
H(OOC)— CH2— COOH  —        CH3— COOH »       CH4 

Malonic  acid  Acetic  acid  Methane 

Thus  the  constitution  of  malonic  acid  is  fully  established  as  di- 
carboxy  methane  or  mono-carboxy  acetic  acid,  in  accordance  with  the 
formula  as  given.  It  is  really  the  first  member  of  the  homologous 
series  of  dicarboxy  caids  as  it  is  the  first  one  that  contains  a  carbon- 
hydrogen  group,  ( — CH2 — ),  just  as  acetic  acid  may  be  regarded  as 
the  first  member  of  the  homologous  series  of  mono-carboxy  acids. 
Formic  acid  and  oxalic  acid,  neither  of  which  contain  a  carbon-hydrogen 
group,  may  be  considered  as  standing  outside  of  the  truly  homologous 
series,  though,  of  course,  they  are  the  simplest  representatives  of  the 
mono-  and  di-  basic  acids. 

Homologues. — By  substituting  methyl  or  higher  alkyl  radicals  into 
the  group  ( — CH2 — )  of  malonic  acid  we  obtain  a  series  of  homologous 
di-basic  acids  just  as  the  homologous  series  of  mono-basic  acids  are 
formed  from  acetic  acid.  Malonic  acid  is  a  solid  crystallizing  in  tri- 
clinic  plates  which  melt  at  132°.  It  is  soluble  in  water  and  in  alcohol. 
It  occurs  in  nature  in  sugar  beets  from  which  source  it  is  obtained  from 
the  incrustation  formed  on  the  evaporating  pans  when  beet  sugar  is 
made. 

Reactions. — An  important  reaction  of  malonic  acid  is  one  that  takes 
place  when  it  is  heated  with  strong  dehydrating  agents,  e.g.,  phosphorus 
pent-oxide,  P2C>5.  Two  molecules  of  water  are  lost  and  carbon  sub- 
oxide,  C3O2,  is  formed,  as  follows: 

CO(OH)  C  =  O 

I  -2H20         II 

C(H)(H)  —  C 

CO(OH)  C  =  O 

Malonic  acid  Carbon  sub-oxide 

Malonic  Acid  Syntheses. — Malonic  acid  is  one  of  the  most  impor- 
tant synthetic  compounds  in  organic  chemistry  as  it  yields  derivatives 


DI-BASIC   ACIDS 


275 


that  are  very  reactive.  The  derivatives  which  are  most  important 
and  which  lend  themselves  to  synthetic  reactions  are  the  esters.  Like 
all  acids  malonic  acid  yields  esters  readily.  As  a  di-basic  acid  it 
yields  both  acid  and  neutral  esters.  It  is  the  latter,  however,  which 
are  the  most  important,  e.g., 

ROOC— CH2— COOR        C2H5OOC— CH2— COOC2H8 

Neutral  malonic  acid  esters  Di-ethyl  malonate 

In  these  reactions  the  characteristic  property  of  malonic  acid  and  its 
esters  rests  in  the  methylene  group,  ( — CH2 — ).  This  same  group  we 
will  recall  is  the  reactive  part  of  aceto  acetic  ester  and  we  shall  find 
that  the  linkage  of  the  group  is  alike  in  the  two  compounds.  When 

a  carbon-hydrogen  group  is  linked  to  two  carbonyl  groups,  (C  =  O),  or 

to  two  carboxyl  groups,  ( — COOH),  the  latter  containing  the  carbonyl 
group,  the  hydrogen  atoms  of  this  carbon-hydrogen  group  possess  dis- 
tinctly acid  properties.  This  acid  character  of  the  hydrogen  atoms  of  a 
methylene  group  so  linked  is  shown  especially  in  the  reaction  with 
metallic  sodium,  or  with  sodium  alcoholate,  as  in  the  case  of  aceto 
acetic  ester  (p.  257).  In  this  reaction  hydrogen  is  liberated  and  the 
sodium  enters  the  methylene  group  in  its  place,  as  follows : 

COOC2H5  COOC2H5  COOC2H6 

I  -H      I  -H     I 

CH2  +  Na   — **     CHNa          +  Na   -    — *     CNa2 

COOC2H5  COOC2H5  COOC2H5 

Di-ethyl  malonate  Mono-sodium  Di-sodium 

di-ethyl  malonate  di-ethyl  malonate 

It  will  be  recalled  that  sodium  compounds  of  the  alkyl  radicals  are 
of  importance  in  the  synthesis  of  hydrocarbons  and  acids. 

CH3— (Na  +  I)— CH3       -r-i     CH3— CH3  +  Nal 

Sodium  methyl  Ethane 

CH3— Na  +  CO2        — >    CH3— COONa 

Sodium  methyl  Sodium  acetate 


276  ORGANIC  CHEMISTRY 

In  the  case  of  malonic  acid  and  other  compounds  when  the  methy- 
lene  group  is  linked  to  two  carboxyl  groups  the  sodium  compounds  are 
more  easily  formed  than  are  the  sodium  compounds  of  the  alkyl  radicals 
themselves.  These  sodium  compounds  of  malonic  acid  ester,  are 
especially  reactive  toward  alkyl  halides  with  the  result  that  the  alkyl 
radical  is  introduced  into  the  malonic  acid  ester  in  place  of  the  sodium, 
i.e.,  in  place  of  hydrogen  of  the  methylene  group.  This  is  shown  by  the 
following  reactions, 

COOC2H5  COOC2H5 

I  I 

CH(Na     +    I)—  CH3       -  >        CH(CH3)     +    Nal 

COOC2H5  COOC2H5 

Mono-sodium  Di-ethyl  ester  of 

di  -ethyl  malonate  methyl  malonic  acid 

Thus,  by  these  reactions,  we  may  introduce  into  malonic  acid  a 
methyl  radical,  or  by  using  any  alkyl  halide,  I  —  R,  we  may  introduce 
any  alkyl  radical.  Now  as  the  esters  by  hydrolysis  yield  the  acids,  and 
the  di-basic  acids  by  loss  of  carbon  dioxide  yield  the  corresponding 
mono-basic  acids,  which  in  turn,  by  loss  of  carbon  dioxide,  yield 
hydrocarbons,  this  general  synthetic  reaction  gives  us  a  means  of 
preparing  either  homologous  di-basic  acids,  corresponding  mono-basic 
acids,  or  the  corresponding  hydrocarbons.  Thus  the  malonic  acid 
syntheses,  or  as  they  are  also  known,  the  malonic  ester  syntheses,  are 
most  important  reactions  for  the  general  synthesis  of  any  mono-basic 
or  di-basic  acid.  Also,  by  reacting  with  halogens  alone,  two  mole- 
cules of  malonic  acid  are  united  into  a  condensation  product  and  another 
type  of  compound,  viz.,  a  tetra-basic  acid  is  formed,  as  follows: 

COOC2Ho  COOC2H5  COOC2H5    COOC2H5 

I  III 

HC(Na        +     I2     +Na)CH  ^HC-  -CH 


COOC2H5  COOC2H5  COOC2H6 

Mono-sodium  di-ethyl  malonate  Tetra-ethyl  ester  of 

tetra-carboxy  ethane 

It  is  probable  that  the  steps  in  these  reactions  take  place  in  a 
different  way  than  that  indicated  and  exactly  analogous  to  the  similar 


DI-BASIC   ACIDS 


277 


reactions  of  aceto  acetic  ester  (p.  255).  The  reaction  is  carried  out  in 
alcohol  and  sodium  alcoholate  is  first  formed.  This  is  then  added  on 
directly  to  the  malonic  acid  ester,  the  addition  product  losing  alcohol 
yielding  a  compound  containing  a  double  bond,  as  follows: 


OC2H5 


CH 


OC2H5 


C2H5O— C— ONa 


+C2H5ONa 


OC2H5 

I 
C— ONa 


-C2H5OH     II 
CH2 »          CH 


COOC2H5 

Di-ethyl 
malonate 


COOC2H5 

Addition  product 


COOCoHg 

Mono-sodium 
di -ethyl  malonate 


By  this  view  the  sodium  malonic  acid  ester  does  not  have  the  same 
constitution  as  the  malonic  acid  ester  itself.  The  sodium  malonic  acid 
ester  containing  a  double  bond  now  reacts  with  the  alkyl  halide  and 
forms  first  an  addition  product  similar  to  the  one  formed  with  the 
sodium  alcoholate  which  then  decomposes  and  yields  the  alkyl  substi- 
tution product  of  the  ester  with  the  constitution  first  given. 


OC2H5 

C— ONa 

CH      -f  CH3I 


COOC2H5 

Mono-sodium 
di-ethyl  malonate 


OC2H5 
I)— C— O(Na 

! 

->      CH(CH3) 
COOC2H5 

Methyl  iodide 
addition  product 


OC2H 


-Nal 

—      CH(CH3) 


COOC2H5 

Di-ethyl  ester  of 
methyl  malonic  acid 


Derivatives. — Of  the  salts  of  malonic  acid  only  the  alkali  metal  salts 
are  soluble.  The  esters  of  malonic  acid  have  been  referred  to  as  the 
most  important  derivatives.  Di-ethyl  malonate  is  a  colorless  insoluble 
liquid  boiling  at  198°.  The  mono-sodium  di-ethyl  ester,  referred  to 
in  the  above  reactions,  forms  white  glistening  crystals.  The  di- 
sodium  di-ethyl  malonate  forms  gall-like  masses  and  is  easily  decom- 


278  ORGANIC  CHEMISTRY 

posed.    The   di-acid   chloride,  malonyl  chloride,  and  the  di-amide, 
malon-amide,  are  both  known. 

Malonyl  chloride,   Cl— OC— CH2— CO— Cl. 
Malon-amide,   H2N— OC— CH2— CO— NH2. 

Malonic  acid  does  not  yield  an  anhydride. 

Homologues  of  Malonic  Acid 

Several  of  the  homologues  of  malonic  acid  are  known  and  they  may 
all  be  prepared  by  the  malonic  ester  synthesis  as  described  above.  A 
few  of  these  will  be  mentioned  simply  by  giving  their  formulas. 

CH(CH3)  =  (COOH)2  Methylmalonic  acid.  Iso-succinic acid. 

CH(C2H5)  =  (COOH)2  Ethyl  malonic  acid. 

CH(C3H7)  =  (COOH)2  Propyl  malonic  acid. 

CH(CH(CH3)2)  =  (COOH)2  Iso-propyl  malonic  acid. 
H3C— C(C2H5)  =  (COOH)2    Methyl-ethyl  malonic  acid. 

Succinic  Acid      HOOC— CH2— CH2— COOH.    Butan-di-oic  Acid 

As  oxalic  acid  is  derived  from  ethan-di-ol,  ethylene  glycol,  and 
malonic  acid  is  derived  from  i-3-propan-di-ol,  so  the  next  member  in 
such  a  series  will  be  derived  from  i-^-butan-di-ol,  as  follows: 

CH2— OH  COOH 

CH2  CH2  CH2— COOH 

I  —  I  or    | 

CH2  CH2  CH2— COOH 

I  I 

CH2— OH  COOH 

i-4-Butan-di-ol  Butan-di-oic  acid      or         Succinic  acid 

Synthesis  from  Ethylene  Bromide. — Such  an  acid  is  known  as  a 
commonly  occurring  substance  in  nature  and  is  called  succinic  acid. 
It  has  the  composition  C4HeO4  and  is  plainly  isomeric  with  methyl 
malonic  acid.  Its  constitution  as  given  above  is,  however,  proven 
by  the  following  syntheses:  Ethylene  bromide,  or  symmetrical  di- 
brom  ethane,  which  is  made  by  the  addition  of  bromine  to  ethylene 
gas,  yields  by  treatment  with  potassium  cyanide  a  symmetrical  di- 


DI-BASIC   ACIDS  279 

cyano  ethane,  or  ethylene  cyanide.     This  compound  is  also  called 
succinic  nitrile  because  it  yields  succinic  acid  on  hydrolysis,  as  follows: 

CH2  CH2— Br  CH2— CN 

+  Br2-— >    |  +  KCN--— >    |  +  4H2O > 

CH2  CH2— Br  CH2— CN 


Ethylene  Ethylene  bromide  Di-cyano  ethane 

Di-brom  ethane  (Sym.)  (Sym.) 


CH2— COOH 


CH2— COOH 

Succinic  acid 
Di-carboxy  ethane  (Sym.) 

Therefore,  succinic  acid  is  symmetrical  di-carboxy  ethane. 

From  Brom  Acetic  Acid. — Also,  mono-brom  acetic  acid,  Br — CH2— 
COOH,  by  the  condensation  of  two  molecules,  with  the  elimination  of 
the  halogen  by  means  of  silver,  yields  succinic  acid,  as  follows : 

HOOC— CH2— Br  +  Br— CH2— COOH  +  2Ag    > 

Mono-brom  acetic  acid 

(2  Molecules) 

HOOC— CH2— CH2— COOH  +  2  AgBr 

Succinic  acid 

Di-acetic  Acid. — By  this  synthesis,  succinic  acid  must  be  two  mole- 
cules of  acetic  acid  joined  together  by  the  loss  of  one  hydrogen  from 
each  molecule.  It  is  therefore  a  symmetrical  compound  consisting  of 
two  like  residues  of  acetic  acid,  ( — CH2 — COOH),  i.e.,  di-acetic  acid. 

From  Malonic  Ester. — The  same  constitution  is  also  proven  by  an 
interesting  synthesis  from  malonic  ester.  Mono-sodium  di-ethyl 
malonate  reacts  with  monobrom,  or  mono-iodo  acetic  acid,  and  yields 
the  ester  of  a  tri-carboxy  acid  which  after  hydrolysis  to  the  acid  loses 
carbon  di-oxide  and  yields  succinic  acid. 

COOR  (COO)R 

!  I  +H20 

CH(Na         +  Br)CH2— COOR  >  CH— CH2— COOR 


Brom  acetic  acid 


-CO 


(Ester) 

COOR|j  COOR 

Mono-sodium 
di-ethyl  malonate 

CH2— CH2— COOH 

I 
COOH 

Succinic  acid 


280  ORGANIC  CHEMISTRY 

Thus,  according  to  these  two  syntheses  succinic  acid  must  be 
symmetrical  di-acetic  acid.  As  succinic  acid  is  isomeric  with  methyl 
malonic  acid  the  latter  is  also  called  iso-succinic  acid. 

Properties. — Succinic  acid  has  been  known  for  a  long  time.  It 
is  quite  widely  distributed  in  nature.  It  is  found  in  unripe  fruits, 
especially  in  grapes,  also  in  lignite,  in  peat  and  in  many  plants.  Its 
most  important  occurrence  is  in  amber  from  which  it  may  be  obtained 
by  distillation.  It  is  also  a  constituent  of  wines  where  it  is  the  product 
of  the  alcoholic  fermentation  of  the  sugars  of  grape  juice.  Another 
source,  which  will  be  considered  later,  is  from  malic  and  tartaric  acids 
by  bacterial  or  mould  fermentation.  Succinic  acid  crystallizes  in 
plates  or  columns  which  melt  at  182°.  It  sublimes  when  it  is  heated 
below  its  melting  point.  When  heated  rapidly  to  235°  it  loses  water 
and  forms  an  anhydride.  It  is  soluble  in  14  parts  of  water. 

Derivatives  of  Succinic  Acid 

Salts. — The  salts  of  succinic  acid  are  not  of  especial  importance 
The  basic  ferric  succinate  is  used  in  the  analytical  separation  of  iron, 
zinc,  manganese,  cobalt  and  nickel.  As  stated  above  when  succinic, 
acid  is  heated  rapidly  to  235°  it  loses  water  and  forms  an  anhydride. 

Anhydride. — In  considering  the  mono-basic  acids  it  was  stated 
that  acetic  acid  formed  an  anhydride  by  the  loss  of  one  molecule  of 
water  from  two  molecules  of  the  acid,  as  follows: 

CH3— CO(OH     _H20     CH3— CO, 

/° 
CH3— COO(H  CH3— C(/ 

Acetic  acid  Acetic  anhydride 

(2  molecules) 

Succinic  acid,  however,  forms  an  anhydride  by  the  loss  of  one  mole- 
cule of  water  from  one  molecule  of  the  acid,  as  follows: 

CH2— CO(OH     _H20     CH2— CO 

I  -       I  > 

CH2— COO(H  CH2—  COT 

Succinic  acid  Succinic  anhydride 

Succinic  anhydride  is  thus  an  inner  anhydride  and  the  open  chain 
compound  is  changed  into  a  ring  or  cyclic  compound.  This  is  of  especial 
importance  in  connection  with  the  relation  between  open  chain  and 
cyclic  compounds  as  will  be  pointed  out  later  when  we  consider  the 


DI-BASIC   ACIDS 


28l 


latter  class.  The  formation  of  this  inner  anhydride  compound  and  of 
a  similar  inner  anhydride,  or  de-ammoniated  compound,  from  the 
amide  of  succinic  acid,  is  of  especial  importance  in  connection  with  the 
tetra-hedral  theory  of  the  carbon  atom.  None  of  the  other  di-basic 
acids  thus  far  mentioned,  viz.,  oxalic  acid  or  malonic  acid,  or  thehomo- 
logues  of  the  latter,  form  these  inner  anhydrides.  When  a  chain  of 
four  tetra-hedral  carbon  groups,  of  which  the  end  carbons  are  car- 
boxyl  groups,  is  constructed  with  models,  or  by  drawings,  it  will  be  seen 
that  the  space  relations  of  the  two  carboxyl  groups  are  such  that  the 
two  hydroxyls  come  very  close  together.  This  is  shown  by  the  accom- 
panying drawing. 


jSuccinic   acid 


)$ucctmc  anhydride 


PIG.  5. 


With  oxalic  acid,  which  has  only  two  carbon  groups,  both  of  which 
are  carboxyl,  or  with  malonic  acid  which  has  three  carbon  groups,  it  is 
found  that  the  hydroxyls  of  the  two  carboxyl  groups  are  some  distance 
apart  and  that  the  tendency  to  lose  water  and  form  anhydrides  does 
not  exist  as  shown  by  the  fact  that  anhydrides  are  not  known.  If  a 
fifth  carbon  group  is  introduced  into  succinic  acid,  as  is  the  case  in 
glutaric  acid,  which  we  shall  presently  consider,  we  find  that  the  two 
carboxyl  groups  at  the  end  of  the  chain  of  five  carbons  practically 
touch  each  other  and  the  formation  of  an  anhydride  in  the  case  of 
this  acid  takes  place  even  more  readily  than  with  succinic  acid.  This 
interesting  space  relation  will  be  considered  again  when  we  come  to  the 
study  of  the  cyclic  compounds.  Succinic  anhydride  may  also  be  formed 


282  ORGANIC  CHEMISTRY 

from  succinic  acid  by  the  action  of  dehydrating  agents,  e.g.,  phosphorus 
oxy-chloride,  POC13,  when  heated  with  it  to  ioo°-i2O°.  Succinic 
anhydride  forms  crystals  which  melt  at  116.5°  and  boil  at  261°.  The 
anhydride  dissolves  in  water  reforming  the  acid. 

Acid  Chlorides.  —  As  succinic  acid  is  a  di-basic  acid  it  forms  a 
di-chloride  when  the  acid,  or  the  anhydride,  is  treated  with  phos- 
phorus penta-chloride,  PCU.  Two  compounds  result,  however;  one, 
which  is  formed  in  much  smaller  amount,  has  been  shown  to  be  analo- 
gous to  the  chloride  of  malonic  acid,,  malonyl  chloride.  It  is  known 
as  the  symmetrical  succinyl  chloride. 

CH2—  COOH  CH2—  COC1 

|  +   PC15  -»  | 

CH2—  COOH  CH2—  COC1 

Succinic  acid  Succinyl  chloride 

(Symmetrical) 

This  symmetrical  succinyl  chloride  is  a  crystalline  compound  which 
melts  at  190°.  By  far  the  greater  part  of  the  product  of  the  action  of 
phosphorus  penta-chloride  upon  succinic  acid  is  not  the  compound 
above  mentioned  but  another  to  which  an  unsymmetrical  formula 
has  been  given,  as  follows: 

CH2—  COOH  CH2—  C=C12  CH2—  C=O 


\) 


+  PC15  -  -»  >0    <-  -  PC15 

CH2—  COOH  CH2—  C=O  CH2—  C= 

Succinic  acid  Succinyl  chloride  Succinic 

(Unsymmetrical)  anhydride 

If  the  reaction  is  written  with  the  anhydride  instead  of  the  acid  itself 
it  will  be  seen  that  the  action  consists  in  two  chlorine  atoms  of  the 
phosphorus  penta-chloride  replacing  one  of  the  carbonyl  oxygens,  of  the 
acid.  This  replacement  of  one  oxygen  by  two  chlorines  is,  we  know,  the 
true  reaction  of  phosphorus  penta-chloride  (p.  81).  We  shall  find, 
also,  that  this  reaction  and  the  unsymmetrical  compound  formed  are 
similar  to  reactions  and  compounds  which  we  shall  consider  in  the 
study  of  the  benzene  di-basic  acid,  phthalic  acid. 

Acid  Amides.  —  Succinic  acid,  like  oxalic  acid,  forms  both  a  mono- 
and  a  di-amide. 

CH2—  COOH   CH2—  COOH    CH2—  CONH2 
CH2—  COpH   CH2—  CONH2   CH2—  CONH2 

Succinic  acid  Succinamic  acid  Succinamide 


DI-BASIC  ACIDS  283 

The  mono-amide,  succinamic  acid,  crystallizes  in  needles  which 
melt  at  156°.  Like  the  di-chloride  the  di-amide  of  succinic  acid  also 
exists  in  two  is  omeric  forms,  viz.,  the  symmetrical  and  the  unsymmetrical. 
When  di-ethyl  succinate  is  treated  with  ammonia,  succinamide  is 
obtained.  This  compound  is  crystalline  and  melts  at  242°. 

CH2—  COOC2H5  CH2—  CONH2 

|  +     2NH3       —  >     |  +     2C2H5OH 

CH2—  COOC2H5  CH2—  CONH2 

Di-ethyl  succinate  Succinamide 

(Symmetrical) 

If,  however,  the  di-amide  is  prepared  by  treating  the  di-chloride 
with  ammonia  another  compound  is  obtained.  As  just  stated,  when 
the  di-chloride  is  prepared  the  product  is  a  mixture  of  two  compounds, 
viz.,  the  symmetrical  and  the  unsymmetrical  succinyl  chlorides.  This 
mixture  of  di-chlorides  yields,  by  treatment  with  ammonia,  a  similar 
mixture  of  the  symmetrical  succinamide,  just  described,  and  another 
compound  which  is  non-crystalline  and  which  melts  at  90°.  To  this 
latter  compound  the  unsymmetrical  structure  has  been  given 


CH2—  0=C12  CH2—  C^ 

|  \)  +     2NH3  -4         |  ) 

CH2—  C^O  CH2—  C=O 

Unsymmetrical  succinyl  chloride  Unsymmetrical  succinamide 

Imide.  —  When  ammonium  acid  succinate  is  heated  water  is  lost  in 
two  steps.  First,  succinamic  acid  is  obtained  and  then  an  anhydride 
compound.  The  same  compound  is  also  obtained  when  the  symmetrical 
di-amide  is  heated  and  a  molecule  of  ammonia  is  lost.  The  compound 
has  been  shown  to  have  an  inner  anhydride  structure  exactly  analogous 
to  succinic  anhydride  and  is  known  as  succin-imide.  The  reactions 
may  be  represented  as  follow: 

CH2—  CO(0)NH2(H2)    _H20   CH2—  CONH(H)   _H2O   CH2—  C^O 

>NH 


CH2— COOH  CH2— CO(OH)  CH2— C=O 

Ammonium  acid  succinate                           Succinamic  acid  Succin-imide 

CH2— CONH(H)                                _NH3  CH2— C=O 

|                                                            >  |  >N 

CH2— CO(NH2)  CH2— C=0 

Succin-amide  Succin-imide 


284  ORGANIC  CHEMISTRY 

The  compound  is  also  formed  by  the  action  of  ammonia  upon  succinic 
anhydride, 

CH2— C=0  CH2— C=0 

|  >(0       +      H2)  =  NH        >  |  >NH  +  H20 

CH2— C=0  CH2— C=0 

Succinic  anhydride  Succin-imide 

Succin-imide  is  soluble  in  water  and  forms  crystals  with  one  mole- 
cule of  water  of  crystallization.  The  water-free  succinimide  melts  at 
1 26°  and  boils  at  288°. 

Homologues  of  Succinic  Acid 

The  homologues  of  succinic  acid  are  analogous  to  those  of  malonic 
acid  and  are  formed  by  the  introduction  of  alkyl  radicals  into  the  carbon 
groups  that  are  not  carboxyl  in  character.  As  succinic  acid  contains 
two  such  carbon  groups,  each  of  which  has  two  replaceable  hydrogens, 
we  may  have  the  introduction  of  one,  two,  three  or  four  alkyl  radicals. 
Taking,  as  an  illustration,  the  methyl  substitution  products  of  succinic 
acid  we  may  have  the  following  compounds: 

CH2— COOH    CH3— CH— COOH    CH3— CH— COOH 
CH2— COOH       HCH— COOH    CH3— CH— COOH 

Succinic  acid  Mono-methyl  Di-methyl  succinic 

succinic  acid  acid 

(CH3)2C— COOH       (CH3)2C— COOH 

I  I 

(CH3)HC— COOH       (CH8)  2C— COOH 

Tri-methyl  succinic  Tetra-methyl 

acid  succinic  acid 

Mono-methyl  succinic  acid  is  known  also  as  pyro-tartaric  acid  as  it  is 
formed  from  tartaric  acid  by  heating.  While  the  mono-,  tri-,  and  tetra- 
methyl  succinic  acids  can  plainly  be  of  only  one  type,  the  di-methyl 
succinic  acid  may  exist  in  the  two  forms,  viz.,  the  symmetrical  and 
unsymmetrical,  as  follows, 

CH3— CH— COOH  (CH3)2— C— COOH 

!  I 

CH3— CH— COOH  H2C— COOH 

Symmetrical  Di-methyl  succinic  acid  Unsymmetrical  Di-methyl  succinic  acid 

Both  of  these  di-methyl  succinic  acids  are  known.  The  symmetrical 
compound  boils  at  197°  and  the  unsymmetrical  at  139°.  On  further 


DI-BASIC   ACIDS  285 

examination  of  the  symmetrical  di-methyl  succinic  acid  formula  it 
will  be  noticed  that  it  possesses  two  asymmetric  carbon  atoms.  Thus 
we  have  two  structurally  isomeric  di-methyl  succinic  acids,  the  sym- 
metrical and  the  unsymmetrical,  and  the  former  exists  also  in  stereo- 
isomeric  forms.  The  discussion  of  such  stereo-isomeric  forms  is  better 
considered  when  we  study  the  related  compound  tartaric  acid  and  further 
consideration  will  be  postponed  until  that  time. 

Glutaric  Acid      HOOC— CH2— CH2— CH2— COOH.    Pentan-di-oic  Acid 

We  began  our  study  of  the  di-basic  acids  with  oxalic  acid  which 
consists  of  two  carboxyl  groups  directly  united.  We  then  took  up 
malonic  acid  in  which  the  two  carboxyl  groups  are  separated  by  one 
methylene  group,  and  the  homologues  of  this  acid  formed  by  sub- 
stituting alkyl  radicals  into  this  methylene  group.  We  considered 
next  succinic  acid  in  which  the  two  carboxyl  groups  are  separated  by 
two  methylene  groups,  and  the  homologues  of  it.  We  shall  now  con- 
sider-di-basic  acids  in  which  the  two  carboxyl  groups  are  separated 
by  more  than  two  methylene  groups.  Oxalic  acid  contains  a  two  carbon 
straight  chain,  malonic  acid  a  three  carbon  straight  chain  and  succinic 
acid  SL  four  carbon  straight  chain.  Therefore,  our  next  acid  to  be  con- 
sidered must  contain  zfive  carbon  straight  chain,  i.e.,  it  must  be  derived 
from  pentane  and  will  be  a  pentan-  di-oic  acid.  As  succinic  acid  is 
structurally  isomeric  with  mono-methyl  malonic  acid  (iso-succinic  acid) 
so  mono-methyl  succinic  acid  has  an  isomeric  compound  of  exactly 
the  same  nature. 

COOH  COOH       COOH 

CH2         CH3— CH         CH2 

I  I  I 

COOH  COOH       CH2 

Malonic  acid  Mono-methyl  malonic  acid  I 

Iso-succinic  acid 

COOH 

Succinic  acid 

CH2— COOH        CH3— CH— COOH        CH2— COOH 

I  I  ! 

CH2— COOH  CH2— COOH       CH2 

Succinic  acid  Mono-methyl  succinic  acid       I 

Pyro-tartaric  acid 

CH2— COOH 

Glutaric  acid 


286 


ORGANIC  CHEMISTRY 


The  isomerism  in  both  of  the  above  cases  is  like  that  between 
branched  chain  and  straight  chain  compounds.  In  one  compound  a 
methyl  group  is  substituted  for  a  hydrogen  atom  in  the  intervening 
methylene  group,  thus  making  a  branched  chain.  In  the  isomeric 
compound  a  new  methylene  group  is  interposed  between  the  carboxyl 
groups,  the  compound  being  derived  from  a  straight  chain  hydrocarbon. 
For  this  reason  the  methyl  malonic  acid  could  be  called  iso-butan-di- 
oic  acid  and  succinic  acid  would  be  normal  butan-di-oic  acid. 

This  new  acid,  isomeric  with  mono-methyl  succinic  acid,  pyro- 
tartaric  acid,  is  known  as  glutaric  acid,  or  systematically,  as  i-5-pen- 
tan-di-oic  acid. 

Synthesis  from  Propane. — The  constitution  of  glutaric  acid  as 
i-5-pentan-di-oic  acid  is  proven  by  its  synthesis  from  i-3-di-cyano 
propane  which  in  turn  is  prepared  from  i-3-di-brom  propane,  as 
follows : 


CH2— Br 

I 
CH2 

I 
CH2— Br 

i-3-Di-brom 
propane 


+  KCN 


CH2— CN 


CH2 


CH2— CN 

i-3-Di-cyano 
propane 


CH2— COOH 


CH2— COOH 

:-5-Pentan-di-oic  acid 
Glutaric  acid 


From  Aceto-acetic  Ester. — Glutaric  acid  may  also  be  made  by 
either  the  aceto-acetic  ester  synthesis  or  by  the  malonic  ester  synthesis, 
as  follows, 
COOC2H5  COOC2H5 


CH2 

I 
CO 


CH(Na  +  I)CH2— CH2— COOC2H5 

/3-Iodo  propionic  ester 

CO 


CH3 

Aceto-acetic 
ester 


CH3 

Sodium 

aceto-acetic 

ester 


COOC2H5 
I 
CH— CH2— CH2— COOC2H5 

I 
CO 

I 

CH3 


DI-BASIC   ACIDS  287 

The  last  product  is  then  decomposed  by  the  acid  hydrolysis  (p.  257) 
yielding  acetic  acid  and  glutaric  acid. 

COOC2H5 

H         CH— CH2— CH2— COOC,H5  — > 

1 + 1 

OH       CO 

'I 
CH3 

COOH  COOC2H5 

I  +       ! 

CH3  CH2— CH2— CH2— COOC2H5 

Acetic  acid  Glutaric  acid  (ester) 

From  Malonic  Ester. — By  the  malonic  ester  synthesis  it  results  from 
the  condensation  of  two  molecules  of  the  malonic  ester  with  di-iodo 
methane,  methylene  iodide,  or  with  form-aldehyde,  and  the  subse- 
quent loss  of  carbon  di-oxide  from  the  condensation  product,  as  follows: 

COOC2H5  COOC2H5 

I  I 

HC— (Na  +  I)— CH2— (I  +  Na)— CH  — > 

I  Mono -sodium 

malonic  ester 

COOC2H5          +J?oedMyelene  COOC2H5 


COOC2H5  COOC2H5 

I  I  +H20 


COOC2H5  COOC2H5 

(COO)H  (COO)H 


-2CO2 

PTT PT-T PT-T 


COOH  .     COOH  COOH       -   COOH 

Glutaric  acid 

Glutaric  Anhydride. — These  two  syntheses  show  the  wonderful 
adaptability  of  the  aceto-acetic  ester  and  the  malonic  ester  syntheses  in 


288  ORGANIC  CHEMISTRY 

the  preparation  of  organic  compounds.  Glutaric  acid  crystallizes  in 
prisms  which  melt  at  97.5°.  It  may  be  distilled  at  290°  but  when 
heated  slowly  it  forms  an  inner  anhydride  similar  to  that  formed  in  the 
case  of  succinic  acid. 

CH2— COOH  CH2— CO 

I                         -H20       I 
CH2  •>       CH2  O 

I  ! 

CEt2— COOH  CH2— CO 

Glutaric  acid  Glutaric  anhydride 

As  explained  when  we  were  discussing  the  formation  of  anhydrides 
in  connection  with  succinic  acid,  this  anhydride  of  glutaric  acid  is  still 
more  easily  formed  because  the  two  hydroxyl  groups  of  the  carboxyls  at 
the  end  of  a  five  carbon  chain  are  very  close  togehter  in  space  when  we 
consider  their  space  relations  according  to  the  tetra-hedral  theory. 
Glutaric  acid  forms  esters  and  also  an  imide  analogous  to  those  formed 
in  the  case  of  succinic  acid.  It  is  found  in  sugar  beet  juice  and  a  de- 
rivative of  it,  viz.,  glutaminic  acid,  or  a-amino  glutaric  acid,  COOH — 
CH(NH2)— CH2— CH2— COOH  (p.  391),  is  obtained  as  one  of  the 
hydrolytic  products  of  proteins.  This  last  is  the  chief  source  of  the 
acid.  The  homologues  of  glutaric  acid  are  analogous  to  those  of  suc- 
cinic acid. 

Higher  Di-basic  Acids 

Adipic  Acid — Of  the  di-carboxy  acids  which  contain  more  than  three 
carbon  groups  between  the  two  carboxyls  we  need  only  mention  two. 
Adipic  acid,  like  glutaric  acid,  is  found  in  the  juice  of  the  sugar  beet. 
Its  systematic  name  is  1-6  hexan-di-oic  acid  and  its  formula  is,  HOOC 
CH2— CH2— CH2— CH2— COOH.  It  may  be  synthesized  by  the 
same  general  methods  as  those  described  in  connection  with  glutaric 
acid.  The  constitution  of  adipic  acid  has  been  proven  by  the  follow- 
ing synthesis  from  /3-iodo  propicnic  acid,  in  which  two  molecules  of 
the  acid  are  condensed  by  means  of  silver. 

HOOC— CH2— CH2— (I     +     2Ag  +  I)— CH2— CH2— COOH     > 

0-Iodo  propionic  acid  (2  molecules) 

HOOC— CH2— CH2— CH2— CH2— COOH  +  2AgI 

Adipic  acid 


DI-BASIC   ACIDS 


289 


Suberic  Acid. — The  other  di-basic  acid  which  we  shall  simply  men- 
tion is  obtained  as  an  oxidation  product  of  cork.  On  this  account  it 
is  known  by  the  name  of  suberic  acid.  It  has  the  composition,  C8Hi4O4, 
and  it  contains  six  methylene  groups  between  the  two  carboxyl  groups. 
The  formula  is 


HOOC— CH2— CH2— CH2—  CH 


CH2— COOH, 

i  -8-Octan-di-oic-acid. 


II.  UNSATURATED  DIBASIC  ACIDS 

The  unsaturated  dibasic  acids  bear  the  same  relation  to  the  saturated 
dibasic  acids,  just  considered,  as  the  unsaturated  mono-basic  acids, 
acrylic  acid,  crotonic  acid,  etc.  (p.  172),  do  to  the  saturated  mono- 
basic acids,  acetic  acid,  etc.  They  are  also  the  oxidation  products  of 
the  unsaturated  hydrocarbons,  alcohols,  and  aldehydes  just  as  oxalic 
and  succinic  acids  are  of  the  corresponding  saturated  compounds.  As 
the  simplest  dibasic  acid  containing  an  ethylene  unsaturated  group  will 
contain  two  carboxyl  groups  and  also  two  doubly  linked  carbon  atoms 
there  must  be  at  least  four  carbons  in  the  compound.  This  compound 
will  therefore  correspond  to  succinic  acid  of  the  saturated  series.  Now 
succinic  acid  may  be  derived  from  either  butane  by  oxidation  or  from 
ethane  by  substitution.  Similarly  the  corresponding  unsaturated  acid 
may  be  derived  from  butene  by  oxidation  or  from  ethene  by  substitution. 
All  of  these  general  relationships  may  be  represented  as  follows: 


Mono-derivatives  SATURATED  SERIES 

COOH        CHO        CH2OH        CH3        CH2OH 


CH2 
CH2 


CH2 
CH2 


CH2 
CH2 


CH3  CH3          CH3 

Butanoic  acid    Butanal         Butanol 
Butyric  acid 


1'J 


CH2        CH2 

!    -  I 

CH2        CH2 


CH3        CH2OH 

Butane  Butan- 

di-ol 


Di-derivatives 
CHO      COOH 

I         ! 

CH2       CH2 
CH2        CH2 

!         I 

CHO      COOH 

Butan-       Butan- 
di-al       di-oic  acid 
Succinic 
acid 


2QO 

COOH 
CH 


CHO 


CH 


ORGANIC  CHEMISTRY 

UNSATURATED  SERIES 
CH2OH        CH3        CH2OH 


CH 


CH 


CH 


CHO      COOH 
CH         CH 


CH 


CH3 

Buten-oic 

acid 

Crotonic 
acid 


CH 


CH3 

Buten-al 


CH 


CH3 

Buten-ol 


CH 


CH3 

Butene 


CH 


CH2OH 

Buten- 
di-ol 


SATURATED  SERIES 
Br 


CH 


CHO 

Buten- 
di-al 


CH 


COOH 

Buten-di- 
oic  acid 
Maleic  and 
Fumaric 
acids 


CN         COOH 


CH 


CH3 

Ethane 


Ethane 


Br 

i-2-Di- 

brom 

ethane 


UNSATURATED  SERIES 
Br 

CH2         CH 


CH, 


COOH 

i-2-Di-car- 
ano         boxy  ethane 
ethane  Succinic 

acid 


CN 

i-2-Di-cy- 


CN 


COOH 


CH          CH 


CH2 

Ethene 


CH 


Br 

i-2-Di- 
brom 
ethene 


CH 

I 


CH 


CN          COOH 

i-2-Di-cy-    i-2-Di-car- 

ano         boxy  ethene 

ethene          Maleic  and 

Fumaric  acids 


Maleic  Acid    HOOC— CH  =  CH— COOH    Fumaric  Acid 

Synthesis  from  Succinic  Acid. — Two  isomeric  acids  are  known  ol 

the  constitution  of  di-carboxy  ethene,  or  buten-di-oic  acid.     They  are 

named  maleic  acid  and  fumaric  acid.    Their  synthesis  from  succinic 

acid  establishes  their  constitution.    Mono-brom  succinic  acid  when 


DI-BASIC   ACIDS  2QI 

heated  with  potassium  hydroxide,  loses  hydrogen  bromide  and  yields 
maleic  acid. 

CH2— COOH  CH(Br)— COOH  -HBr 

|  +Br2        — >     HBr  +    |  +  KOH - 

CH2— COOH  CH(H)— COOH 

Succinic  acid  Mono-brom  siiccinic  acid 

CH— COOH 

I! 

CH— COOH 

Maleic  acid 
Fumaric  acid 

Also  di-brom  succinic  acid  loses  two  atoms  of  bromine  and  likewise 
yields  maleic  acid. 

CH(Br)— COOH)  _2  Br      CH— COOH 

!  +  KOH  -7f        j| 

CH(Br)— COOH  CH— COOH 

Di-brom  succinic  acid  Maleic  acid 

Fumaric  acid 

This  synthesis  is  exactly  analogous  to  the  formation  of  the  mono- 
basic unsaturated  acid,  acrylic  acid,  from  beta-brom  propionic  acid, 
or  from  alpha-beta-di-brom  propionic  acid  (p.iy2  ). 

CH(H)— COOH    (_HBr)    CH— COOH     (_2Br)     CH(Br)— COOH 
CH2(Br)  CH2  CH2(Br) 

/3-Brom  propionic  acid  Acrylic  acid  a-/3-Di-brom  propionic  acid 

The  reverse  of  these  reactions:  viz.,  the  conversion  of  maleic  and 
fumaric  acids,  by  the  addition  of  hydrogen  bromide,  into  mono-brom 
succinic  acid;  by  the  addition  of  two  bromine  atoms,  into  di-brom 
succinic  acid;  and  also  by  the  addition  of  two  hydrogen  atoms,  into 
succinic  acid  itself;  all  show  these  same  relations  of  maleic  and  fumaric 
acids  to  succinic  acid  and  its  bromine  substitution  products  and  estab- 
lish the  constitution  of  these  isomeric  di-basic  unsaturated  acids  as 
given.  The  two  acids  may  also  be  prepared  from  malic  acid  which  is, 
in  fact,  the  chief  method  by  which  they  are  prepared.  This  reaction 
will  be  considered  later  when  malic  acid  itself  is  studied. 

Isomerism  of  Maleic  and  Fumaric  Acids. — The  isomerism  of 
maleic  and  fumaric  acids  is  stereo-isomerism  of  the  geometric  type.  It 
is  exactly  like  that  of  the  two  crotonic  acids  (p.  177). 


2Q2  ORGANIC  CHEMISTRY 

H— C— COOH  H— C— COOH 

II  and  || 

H— C— CH3  H3C— C— H 

Crotonic  acid  Iso-crotonic  acid 

(cis)  (trans) 

H— C— COOH  H— C— COOH 

II  and  || 

H— C— COOH  HOOC— C— H 

Maleic  acid  Fumaric  acid 

(cis)  (trans) 

The  proof  that  maleic  acid  corresponds  to  the  cis  formula  and 
fumaric  acid  to  the  trans  formula  is  in  the  fact  that  maleic  acid  readily 
forms  an  anhydride  while  fumaric  acid  does  not.  If  the  two  carboxyl 
groups  are  on  the  same  side,  as  in  the  cis  form,  the  compound  would 
have  a  tendency  to  lose  water  easily;  while  if  the  two  carboxyl  groups 
are  on  opposite  sides,  as  in  the  trans  form,  the  compound  would  not 
have  this  tendency  to  lose  water.  The  space  relations  of  the  two 
carboxyl  groups  is  readily  seen  if  the  two  compounds  are  built  up  by 
means  of  tetra-hedral  models.  It  is  analogous  to  that  in  succinic  acid 
and  glutaric  acid  (p.  281). 


CH2— COOH     CH2— CO   H— C— COOH      H— C— CO 


-H2O 


\ 


o 


-H2O 


0 


/ 

CH2— COOH     CH2— CO   H— C— COOH      H— C— CO 

Succinic  acid  Succinic  Maleic  acid  Maleic 

anhydride  anhydride 

Conversion  of  Maleic  Acid  and  Fumaric  Acid  into  Each  Other.— 

The  conversion  of  maleic  and  fumaric  acids  into  each  other  is  an  ex- 
ceedingly interesting  and  important  relation.  When  fumaric  acid  is 
strongly  heated  above  200°  no  anhydride  of  fumaric  acid  is  formed,  as 
has  been  stated,  but  maleic  anhydride  is  obtained.  On  the  other  hand, 
when  maleic  acid  is  heated  above  its  melting  point,  or  when  it  is  heated 
under  pressure  to  130°,  it  is  converted,  little  by  little,  into  fumaric 
acid.  Also,  when  maleic  acid  is  treated  with  concentrated  hydrochloric 
acid  at  10°,  or  with  hydrobromic  acid  at  o°,  or  boiled  with  hydriodic 
acid,  it  is  likewise  converted  into  fumaric  acid.  When  maleic  anhy- 
dride is  distilled  with  phosphorus  penta-chloride  the  di-chloride  of 
fumaric  acid,  fumaryl  chloride,  results.  These  transformations  show 


DI-BASIC   ACIDS 


293 


the  close  relation  which  the  two  acids  bear  to  each  other  and  will  be 
readily  seen  to  be  dependent,  probably,  upon  their  stereo-chemical 
character.  It  will  be  out  of  place,  in  this  study,  to  discuss  more  fully 
the  processes  by  which  these  reciprocal  transformations  are  effected. 
For  these  discussions  the  student  is  referred  to  such  books  as  Cohen, 
and  Meyer  and  Jacobson. 

Maleic  acid  crystallizes  in  rhombic  prisms  which  melt  at  130°  and 
begin  to  boil  and  lose  water  forming  the  anhydride  at  160°.  The  acid 
is  easily  soluble  in  water.  The  anhydride  crystallizes  in  thin  prisms 
which  melt  at  53°  and  boil  at  202°.  The  chief  method  of  obtaining 
maleic  acid,  as  has  been  said,  is  by  heating  malic  acid.  This  has  given 
to  the  acid  its  name  of  maleic. 

Fumaric  acid  occurs  naturally  in  many  plants,  especially  in  Fumaria 
vulgaris,  from  which  it  derives  its  name.  It  is  also  found  in  some 
fungi.  From  concentrated  solution  it  crystallizes  in  fine  needles. 
When  heated  to  200°  it  volatilizes  and  at  higher  temperatures  is  trans- 
formed into  maleic  anhydride.  It  is  difficultly  soluble  in  water. 

Citra -conic,  Mesa-conic  and  Ita-conic  Acids 

The  only  homologous  unsaturated  di-basic  acids  which  we  shall 
consider  are  those  formed  by  substituting  methyl  for  one  of  the  non- 
hydroxy  hydrogen  atoms,  in  maleic  acid  and  in  fumaric  acid.  Plainly 
each  of  these  two  acids  should  yield  a  methyl  substitution  product  and 
those  two  products  should  differ  from  each  other  just  as  the  maleic 
and  fumaric  acids  differ,  i.e.,  they  should  be  geometric  isomers.  The 
formulas,  corresponding  to  those  of  maleic  and  fumaric  acids,  are 

H3C— C— COOH  H3C— C— COOH 

II  and  || 

H— C— COOH  HOOC— C— H 

Methyl  maleic  acid  Methyl  fumaric  acid 

Citra-conic  acid  Mesa-conic  acid 

Citra-conic  and  Mesa -conic  Acids. — Two  such  geometrically  isomeric 
acids  are  known  to  which  the  names  citra-conic  acid  and  mesa-conic 
acid  have  been  given.  Citra-conic  acid  melts  at  80°  and  easily  yields 
an  anhydride.  It  must,  therefore,  be  represented  by  the  cis  formula 
and  is  the  methyl  derivative  of  maleic  acid.  Mesa-conic  acid  melts 
at  202°  and  does  not  yield  an  anhydride.  It  should,  therefore,  be 


294 


ORGANIC  CHEMISTRY 


represented  by  the  trans  formula  and  is  the  methyl  derivative  of  fumaric 
acid.  The  two  acids  are  obtained  from  citric  acid  which  we  shall 
study  later,  and  from  which  the  former  derives  its  name.  Citra-conic 
acid  and  mesa-conic  acid  are  reciprocally  transformed  into  each  other  as 
in  the  case  of  maleic  and  fumaric  acids.  By  the  addition  of  hydrogen 
they  are  each  converted  into  the  corresponding  saturated  acid,  viz., 
methyl  succinic  or  pyrotartaric  acid.  By  the  addition  of  hydrobromic 
acid  they  each  yield  methyl  brom  succinic  acid,  2-brom  3 -methyl 
butan-di-oic  acid,  and  the  addition  of  bromine  converts  them  each 
into  methyl  di-brom  succinic  acid,  2 -methyl  2-3-di-brom  butan- 
di-oic  acid.  Thus  their  relationship  to  succinic  acid  and  to  maleic 
and  fumaric  acids  is  fully  established  and  their  constitution  proven. 
Ita-conic  Acid. — There  is,  however,  a  third  acid  known  of  the  same 
composition  as  the  two  preceding.  It  is  called  ita-conic  acid  and  like 
the  others  is  obtained  from  citric  acid  by  distillation.  More  than  the 
two  isomers  just  explained  are  not  possible  according  to  geometric  iso- 
merism.  The  isomerism,  therefore,  of  this  new  acid  with  the  other  two 
must  be  explained  in  some  other  way  and  has  been  shown  to  be  struc- 
tural isomerism  due  to  the  different  position  of  the  double  bond.  We 
have  spoken  of  the  fact  that  both  citra-conic  and  mesa-conic  acids, 
by  the  addition  of  hydrogen,  are  converted  into  methyl  succinic  acid. 
This  same  result  is  obtained  with  ita-conic  acid  also  as  may  be  explained 
by  the  following  reactions, 


CH3— C— COOH 

II 
H— C— COOH 

Citra-conic  acid 


CH3— C— COOH 


or 


HOOC— C— H 

Mesa-conic  acid 


+H2 


CH3— CH— COOH 


CH2=C—  COOH 


CH2— COOH 

Methyl  succinic  acid 

CH3— CH— COOH 


H2C—  COOH 

Ita-conic  acid 


CH2— COOH 

Methyl  succinic  acid 


In  this  case  the  products  are  all  the  same  but  if  hydro-bromic  acid 
or  bromine  is  added  the  products  are  different  in  the  case  of  ita-conic 


HYDROXY   DI-BASIC   ACIDS  295 

acid.     Citra-conic  and  mesa-conic  acids  with  hydrobromic  acid  yield, 
2-brom  ^-methyl  butan-di-oic  acid, 

CH3—  C—  COOH  CH3—  C—  COOH 

||  or  ||  +HBr        -r» 

H—  C—  COOH  HOOC—  C—  H 

Citra-conic  acid  Mesa-conic  acid  prr  _  pTj  _  r"OOH 


CHBr—  COOH 

2-Brom  3-methyl  butan- 
di-oic  acid 

Ita-conic  acid,  however,  yields  2-(brom-methyl)  butan-di-oic  acid. 

CH2  =  C—  COOH  BrH2C~CH—  COOH 

|  +  HBr     -  >  | 

H2C—  COOH  H2C—  COOH 

Ita-conic  acid  2-(brom-methyl)- 

butan-di-oic  acid 

The  constitution  of  ita-conic  acid  as  methylene  succinic  acid  is 
thus  established.  Di-basic  acids  which  contain  a  triple  bond  and, 
therefore,  related  to  propin-oic  acid  are  known  but  will  not  be  considered. 


III.  HYDROXY  DI-BASIC  ACIDS 

We  come  now  to  the  study  of  the  substituted  di-basic  acids.  Of  the 
compounds  derived  from  the  di-basic  acids  by  substitution  in  the  car- 
bon-hydrogen groups,  only  those  obtained  by  substituting  the  hydroxyl 
group  will  be  considered  at  this  time.  The  corresponding  amino 
substitution  products  are  of  importance  but  they  will  be  considered 
later  together  with  amino  acids  derived  from  the  mono-basic  acids.  The 
other  classes  of  substitution  products,  e.g.,  halogen,  cyanogen,  etc.,  are 
not  of  importance  by  themselves  but  will  be  taken  up  in  connection 
with  compounds  to  which  they  are  directly  related.  As  oxalic  acid, 
the  first  di-basic  acid  which  we  considered,  has  no  carbon  group  other 
than  carboxyl,  it  is  impossible  to  obtain  from  it  a  substitution  product. 
Therefore,  the  first  di-basic  acid  to  yield  substitution  products  is 
malonic  acid. 


296  ORGANIC  CHEMISTRY 

HYDROXY  MALONIC  ACIDS 
Tartronic  Acid        HOOC-CH(OH) -COOH        Mono-hydroxy  Malonic  Acid 

Synthesis  from  Malonic  Acid. — Tartronic  Acid  is  obtained  from 
malonic  acid  directly  through  mono-chlor  malonic  acid, 

COOH  COOH  COOH 

I  !  I 

CH2        >          CHC1        +AgOH        — >      CH(OH) 

I  I  I 

COOH  COOH  COOH 

Malonic  acid  Mono-chlor  Mono-hydroxy  malonic 

malonic  acid  acid  (Tartronic  acid) 

From  Glycerol. — This  synthesis  shows  tartronic  acid  to  have  the 
constitution  given,  i.e.,  mono-hydroxy  malonic  acid.  It  may  also  be 
obtained  from  glycerol  by  oxidation.  In  this  reaction  the  two  primary 
alcohol  groups  in  glycerol  are  both  oxidized  to  carboxyl  while  the 
secondary  alcohol  group  remains  unchanged. 

CH2OH  COOH 

I  +0  I 

CH(OH)  —  CH(OH) 

I  I 

CH2OH  COOH 

Glycerol  Tartronic  acid 

Mesoxalic  Acid      HOOC— C(OH)2— COOH     Di — hydroxy  Malonic  Acid 

We  have  often  referred  to  the  fact  that  two  hydroxyl  groups  linked 
to  the  same  carbon  yield  compounds  that  are  unstable  and  which  by  loss 
of  water  are  converted  into  other  compounds  which  are  stable.  In  the 
case  of  the  hydroxyl  derivatives  of  malonic  acid  we  have  an  exception 
to  this  rule,  for  di-brom  malonic  acid  yields  with  silver  hydroxide  a 
compound  which  probably  has  the  formula  of  a  di-hydroxy  malonic  acid. 
As  such  substituted  hydroxyl  groups  must,  in  malonic  acid,  be  united 
to  the  same  carbon  atom,  and  the  compound  formed  is  a  stable  one,  we 
either  have  an  exception  to  the  above  given  general  rule  or  we 
must  explain  the  constitution  of  the  resulting  compound  in  some 
other  way. 


HYDROXY   DI-BASIC.  ACIDS  2Q7 

COOH  COOH  COOH  COOH 

I  I  I  -H20     I 
CH2          ***  CBr2  +  2AgOH  >   C(OH)2  or        -- »     C  =  O 

II  II 
COOH            COOH                            COOH  COOH 

Malonic  acid  Di-brom  Di-hydroxy  malonic  acid 

malonic  acid  Mesoxalic  acid 

According  to  one  formula  mesoxalic  acid  has  the  constitution  of  a 
normal  di-hydroxy  malonic  acid  contrary  to  what  we  should  expect. 
According  to  the  second  formula  it  is  a  ketone  acid,  an  anhydride  of  the 
first.  It  should  be  recalled  here  that  in  connection  with  glyoxylic  acid 
(p.  252)  we  emphasized  the  fact  that  in  chloral  hydrate  (p.  226)  and  in 
glyoxylic  acid  we  have  a  carbon  atom  linked  to  a  strongly  negative 
group,  viz.,  ( — CC13)  or  ( — COOH).  In  mesoxalic  acid  the  same 
condition  is  present  only  in  this  case  it  is  doubled. 


H  H  OH 

I  I         -CO2        "I 

CC13— C— OH     HO— C— COOH   « —    HOOC— C— COOH 


OH  OH  OH 

Chloral  hydrate  Glyoxylic  acid  Mesoxalic  acid 

Under  such  conditions  two  hydroxyl  groups  may  be  linked  to  this  car- 
bon forming  a  stable  compound.  Also  mesoxalic  acid  by  loss  of  (CO2) 
by  heat  yields  glyoxylic  acid,  as  above. 

It  should  be  stated  that  the  evidence  is  not  complete  and  the  con- 
stitution of  mesoxalic  acid  is  generally  accepted  as  not  yet  established. 

HYDROXY  SUCCINIC  ACIDS 

The  other  hydroxy  di-basic  acids  which  we  shall  consider  are  the 
hydroxyl  substitution  products  of  succinic  acid.  These  hydroxy 
succinic  acids  are  commonly  occurring  substances  and,  both  from  the 
standpoint  of  theory  and  of  practical  value,  are  most  important  com- 
pounds. The  mono-hydroxy  succinic  acid  is  commonly  known  as 
malic  acid,  and  the  di-hydroxy  compound  is  the  common  substance, 
tartaric  acid. 

CH(OH)— COOH 

Malic  Acid  Mono-hydroxy  Succinic  Acid 

CH2 COOH 


298  ORGANIC  CHEMISTRY 

Relation  to  Succinic  Acid.— The  constitution  of  malic  acid  is  fully 
established  by  its  relation  to  succinic  acid.  It  may  be  synthesized 
from  mono-brom  succinic  acid  by  treatment  with  silver  hydroxide. 

CH2— COOH              CHBr— COOH 
|          +  Br     ->    |  +  AgOH 

CHo— COOH  CH2 COOH  ; 

Succinic  acid  Mono-brom. 

succinic  acid 

CH(OH)— COOH 
CH2         -COOH 

Mono-hydrozy  succinic 
acid.    Malic  acid 

The  reverse  of  this  reaction  takes  place  when  malic  acid  is  heated 
with  hydrobromic  acid,  i.e.,  malic  acid  is  thus  converted  into  mono- 
brom  succinic  acid. 

CH(OH)— COOH               CHBr— COOH 
|             +  HBr     -*    | 
CH2—  -COOH  CH2 COOH 

Malic  acid  Mono-brom  succinic  acid 

When  malic  acid  is  warmed  with  phosphorus  penta-chloride  it 
yields  chlor  succinic  acid,  and  when  reduced  by  means  of  hydrogen 
iodide,  hydrogen  is  added  and  succinic  acid  results. 

CH(OH)— COOH  CHC1— COOH 

|  -f  PC15  — »          |  and 

CH2—     -COOH  CH2—  COOH 

Malic  acid  Chlor  succinic  acid 

CH  (OH)— COOH  CH2— COOH 

+  H2     --> 
CH2—  -COOH  CH2— COOH 

Malic  acid  Succinic  acid 

Relation  to  Maleic  and  Fumaric  Acids. — The  constitution  of 
malic  acid  is  also  proven  by  its  relation  to  maleic  and  fumaric  acids. 
It  was  mentioned,  under  maleic  acid,  that  this  acid  received  its  name 
from  the  fact  that  it  was  obtained  by  heating  malic  acid.  The  reac- 


HYDROXY    DI-BASIC   ACIDS  299 

tion  consists  in  the  loss  of  a  molecule  of  water  from  the  malic  acid. 
The  reverse  reaction  may  also  be  accomplished  by  heating  maleic  or 
fumaric  acids  in  a  sealed  tube  with  water.  The  two  reactions  are  as 
follows : 

CH(OH)— COOH    -H2O    CH— COOH 
CH(H): — COOH    +  H2O    CH— COOH 

Malic  acid  Maleic  acid 

The  loss  of  water  from  hydroxy  acids  and  the  formation  of  unsatu- 
rated  acids  has  been  met  with  before  in  connection  with  the  beta-hydroxy 
mono-basic  acids,  e.g.,  hydraciylic  acid,  /3-hydroxy  propionic  acid,  and 
its  conversion  into  acrylic  acid,  propenoic  acid  (p.  172).  In  such  cases 
the  beta-hydroxy  acid  loses  water  from  two  neighboring  carbon  groups 
thereby  creating  a  double  bond. 

CH2(OH)— CH(H)— COOH         H52_?        CH2  =  CH— COOH 

/3-Hydroxy  propionic  acid  Acrylic  acid 

Hydracrylic  acid 

In  malic  acid  the  hydroxyl  group  is  in  the  beta-position  in  relation 
to  one  of  the  carboxyl  groups  and  the  formation  of  an  unsaturated  acid 
by  the  loss  of  water  would  be  expected. 

Stereo  Isomerism  of  Malic  Acid. — On  examination  of  the  formula 
of  malic  acid  it  will  be  seen  that  one  of  the  carbons  is  asymmetric,  i.e., 
it  has  united  to  it  four  different  elements  or  groups,  viz.,  ( — H),  ( — OH), 
(—COOH),  and  (— CH2— COOH).  We  should,  therefore,  expect  to 
find  that  malic  acid  is  optically  active  and  that  it  exists  in  the  three 
forms  of  dextro,  levo,  and  inactive.  This  is  in  accordance  with  the  facts. 
The  formulas  for  the  three  stereo-isomeric  forms  of  malic  acid  may  be 
written  as  follows,  corresponding  exactly  to  those  for  lactic  acid. 

H  H 

I 
HO— C— COOH  HOOC— C— OH  Malic  acid 

CH2— COOH  CH2— COOH 

Dextro  Levo 


Inactive 


300  ORGANIC  CHEMISTRY 

H  H 


HO— C— COOH        HOOC— C— OH        Lactic  acid 

CH3  CH3 

Dextro  Levo 


Inactive 

The  study  of  malic  acid  in  connection  with  its  stereo-isomerism, 
together  with  the  similar  study  of  the  related  acids,  lactic,  tartaric, 
maleic  and  fumaric  has  been  of  the  greatest  importance  in  establishing 
our  ideas  of  stereo-isomerism. 

Active  Malic  Acid. — Malic  acid  occurs  widely  distributed  in  na- 
ture. It  is  found  partly  free  and  partly  combined,  in  unripe  apples, 
from  which  it  derives  its  name,  in  unripe  mountain  ash  berries,  in 
cherries,  grapes,  goose-berries,  quinces  and  other  fruits.  It  is  found 
as  the  calcium  salt  in  sumach  berries,  in  tobacco  leaves  and  in  maple 
sap  from  which  it  separates  as  a  fine  crystalline  sediment  obtained  when 
the  syrup  is  filtered.  The  free  acid  crystallizes  in  tufts  of  glistening 
deliquescent  needles  which  melt  at  100°.  When  heated  to  i2O°-i3O° 
it  loses  water  and  is  converted  into  maleic  and  fumaric  acids.  It  is 
easily  soluble  in  water  or  in  alcohol.  The  natural  malic  acid,  in 
crystalline  form,  or  in  concentrated  solution,  is  dextro  rotatory.  The 
optical  rotation,  however,  changes  with  the  concentration  of  the  solu- 
tion. In  dilute  solution,  up  to  34  per  cent.,  at  20°,  it  is  levo  rotatory. 
At  this  concentration  it  becomes  inactive  but  if  the  concentration  is 
increased  it  becomes  dextro  rotatory.  In  solution  in  acetone  malic  acid 
is  levo  rotatory.  When  levo  malic  acid  is  treated  with  phosphorus 
penta-chloride,  according  to  the  reaction  previously  given,  chlor  succinic 
acid  is  obtained,  but  it  is  the  dextro  form  which  results,  and  when  this 
dextro  chlorsuccinic  acid  is  converted  back  into  malic  acid,  by  means 
of  silver  hydroxide,  we  obtain  dextro  malic  acid.  Thus  we  have  a 
means  of  converting  the  levo  into  the  dextro  form.  Also,  if  dextro 
malic  acid  is  acidified  with  sulphuric  acid  levo  malic  acid  is  formed.  We 
may  also  obtain  the  dextro  malic  acid  by  the  reduction  of  dextro  tar- 
taric acid,  as  we  shall  see  later. 

Inactive  Malic  Acid. — When  malic  acid  is  prepared  synthetically, 
from  inactive  compounds,  we  obtain  the  inactive  malic  acid.  Thus, 


HYDROXY   DI-BASIC    ACIDS  301 

inactive  bromsuccinic  acid,  inactive  amino  succinic  acid  and  inactive 
tartaric  acid,  (racemic  acid),  all  yield  the  inactive  form  of  malic  acid. 
Also,  by  the  reaction  previously  given,  by  heating  maleic  acid  in  a  sealed 
tube  with  water,  inactive  malic  acid  results.  The  inactive  malic  acid 
may  be  split  into  its  optical  components  by  proper  reactions  as  was  dis- 
cussed under  lactic  acid  and  as  will  be  again  mentioned  in  connection 
with  tartaric  acid.  Inactive  malic  acid  crystallizes  easily,  is  not  de- 
liquescent and  is  less  soluble  than  ordinary  active  malic  acid. 

CH(OH)— COOH 

Tartaric  Acid  Di-hydroxy  Succinic  Acid 

CH(OH)— COOH 

By  the  introduction  of  one  more  hydroxyl  group  into  malic  acid 
we  obtain  a  di-hydroxy  succinic  acid  which,  as  a  di-hydroxy  compound, 
is  analogous  to  mesoxalic  acid  and  bears  the  same  relation  to  succinic 
acid  and  to  malic  acid  that  mesoxalic  acid  bears  to  malonic  acid  and  to 
tartronic  acid.  The  acid  of  this  constitution  is  the  commonly  occur- 
ring substance  tartaric  acid..  That  tartaric  acid  contains  two  carboxyl 
groups  and  at  the  same  time  two  alcohol  hydroxyl  groups  and  that  it 
is  in  fact  di-hydroxy  succinic  acid  is  proven  by  several  syntheses  and 
reactions. 

Di-basic  and  Di-alcoholic.— That  tartaric  acid  is  di-basic,  i.e., 
that  it  contains  two  carboxyl  groups  is  shown  by  the  fact  that  it  forms 
di-alkyl  esters  and  di-metal  salts. 

C2H2(OH)2(COOK)2,       C2H2(OH)2(COOH)2,        C2H2(OH)2(COOR)2 

Di-potassium  salt  Tartaric  acid  Di-alkyl  ester 

That  it  contains  two  alcohol  hydroxyl  groups  is  proven  by  the  fact 
that  its  di-alkyl  esters  form  di-acetyl  derivatives, 

C2H2(OH)2(COOR)2        >        C2H2(OOC— CH3)2(COOR)2 

Di-alkyl  ester  Di-acetyl  di-alkyl  ester 

Symmetrical. — Two  formulas  are,  however,  possible  for  a  di- 
hydroxy  succinic  acid,  viz.,  the  symmetrical  and  the  unsymmetrical. 

CH  (OH)— COOH  C  (OH)  2— COOH 

CH(OH)— COOH  CH2— COOH 

Di-hydroxy  succinic  acid  Di-hydroxy  succinic  acid 

Symmetrical  Unsymmetrical 


302  ORGANIC  CHEMISTS Y 

That  tartaric  acid  is  not  the  unsymmetrical  di-hydroxy  succinic 
acid  is  shown  by  the  fact  that  an  acid  of  this  constitution  would,  by 
loss  of  water,  yield  a  ketone  acid,  as  follows: 

C(OH)2— COOH  CO— COOH 

|  -H20       -->        | 

CH2— COOH  CH2— COOH 

Unsymmetrical  formula  Ketone  acid 

Such  an  acid  as  this  ketone  acid  is  known  and  is  called  oxal  acetic 
acid,  and  tartaric  acid  does  not  yield  this  acid  on  heating  nor  does  it 
show  any  properties  of  a  ketone  acid.  We,  thus,  have  no  evidence 
that  tartaric  acid  is  the  unsymmetrical  di-hydroxy  succinic  acid.  That 
tartaric  acid  is,  in  fact,  the  symmetrical  di-hydroxy  succinic  acid  is 
proven  by  its  synthesis  from  glyoxal,  and  also  by  its  synthesis  from 
succinic  acid  itself. 

Synthesis  from  Glyoxal. — Glyoxal,  being  a  di-aldehyde,  (p.  261), 
forms  a  di-addition  product  with  hydrogen  cyanide,  HCN,  and  this 
di-cyanide  addition  product  hydrolyzes  and  yields  tartaric  acid.  The 
reaction  may  be  expressed  as  follows, 

H  H  H 

I  I 

0  =  C  HO— C— CN  HO— C— COOH 


2HCN 


+4H20 


O  =  C  HO— C— CN          HO— C— COOH 

I  I  I 

H  H  H 

Glyoxal  Glyoxal  di-cyan  Tartaric  acid 

hydrine 

According  to  this  synthesis  tartaric  acid  must  have  the  two  hydroxyl 
groups  linked  to  different  carbon  atoms,  and  also  the  two  carboxyl 
groups  must  likewise  be  linked  to  different  carbon  atoms  and  further- 
more each  carbon  of  the  original  glyoxal  must  have  one  hydroxyl  group, 
one  carboxyl  group  and  one  hydrogen  atom  linked  to  it.  It  must  there- 
fore be  the  symmetrical  compound. 

From  Succinic  Acid. — The  synthesis  of  tartaric  acid  from  succinic 
acid  also  proves  that  it  must  be  the  symmetrical  di-hydroxy  succinic 
acid.  When  succinic  acid,  by  means  of  bromine,  yields  the  symmetrical 
di-brom  succinic  acid  this,  in  turn,  when  treated  with  silver  hydroxide, 


HYDROXY   DI-BASIC   ACIDS 


303 


has  the  two  bromine  atoms  replaced  by  two  hydroxyl  groups,  and  tar- 
taric  acid  results, 

CH2— COOH  CHBr— COOH 

|  +     Br        — »      |  +     AgOH      > 

CH2— COOH  CHBr— COOH 

Succinic  acid  Di-brom  succinic 

acid 

(Symmetrical") 

CH(OH)— COOH 
CH(OH)— COOH 

Di-hydroxy  succinic 

acid,  (symmetrical) 

Tartaric  acid 

From  Malic  Acid. — Another  synthesis  of  tartaric  acid  is  from 
malic  acid.  When  malic  acid  is  treated  with  bromine  it  yields  a  mono- 
brom  malic  acid  which  by  means  of  calcium  hydroxide  yields  tartaric 
acid. 

CH(OH)— COOH         CH(OH)— COOH 

|            +Br  -  ->  |  +Ca(OH)2  -  -> 

CH2 COOH          CHBr COOH 

Malic  acid  Mono-brom  malic  acid 

CH(OH)— COOH 
CH(OH)— COOH 

Tartaric  acid 

From  Maleic  and  Fumaric  Acids. — Still  another  synthesis  is  from 
maleic  and  fumaric  acids.  When  these  acids  are  cautiously  oxidized 
by  means  of  potassium  permanganate  or  chamelion  solution  water  and 
oxygen  are  added  to  the  unsaturated  acids  and  the  product  is  tartaric 
acid. 

CH— COOH  CH(OH)— COOH 

||  +     H20     +     O       -»      ! 

CH— COOH  CH(OH)— COOH 

Maleic  acid  Tartaric  acid 

Fumaric  acid 

Reduction  to  Malic  and  Succinic  Acids. — The  relation  of  tartaric 
acid  to  malic  acid  and  to  succinic  acid  is  shown,  also,  by  the  conversion 
of  tartaric  acid  into  each  of  these  acids  successively,  which  is,  in  fact, 
more  easily  accomplished  than  the  reverse  reactions  just  described. 


304  ORGANIC  CHEMISTRY 

By  reduction  with  hydrogen  iodide,  tartaric  acid  yields,  first,  malic 
acid,  and  then  succinic  acid, 

CH(OH)— COOH       (HI)  CH(OH)— COOH       (HI) 

|  +  H2  >   |  +  H2   -» 

CH(OH)— COOH  CH2 COOH 

Tartaric  acid  Malic  acid 

CH2— COOH 

I 
CH2— COOH 

Succinic  acid 

Isomerism  of  Tartaric  Acid. — Examination  of  the  formula  for 
tartaric  acid,  which,  by  the  facts  given  above,  has  its  constitution  fully 
established  as  symmetrical  di-hydroxy  succinic  acid,  shows  the  interest- 
ing fact  that  there  are  present  two  asymmetric  carbon  atoms,  and  that 
each  of  these  has  linked  to  it  the  same  set  of  four  different  groups.  We 
should,  therefore,  expect  to  find  tartaric  acid  existing  in  the  dextro,  the 
lew  and  the  inactive  forms.  The  stereo-chemical  formulas  similar  to 
those  of  lactic  and  malic  acids  we  may  write  as  follows, 

Tartaric  Acid 

H  OH 

I  I 

HO— C— COOH  H— C— COOH 

H— C— COOH  HO— C— COOH 

OH  H 

Dextro  Levo 


Inactive 

One  of  the  above  formulas  may  be  taken  to  represent  the  dextro 
form  and  the  other  the  levo.  The  mixture  of  the  two  will  produce  the 
inactive  acid.  Now  these  three  forms  of  tartaric  acid  are  all  known  and 
they  bear  to  each  other  exactly  the  same  relation  as  has  been  explained 
in  connection  with  lactic  acid.  The  inactive  form  is  able  to  be  split 
into  its  two  optical  components  like  the  inactive  lactic  acid.  These 
three  acids  are  as  follows, 

Dextro  Tartaric  Acid. — The  ordinary  tartaric  acid  as  it  occurs  in 
grapes. 


HYDROXY   DI-BASIC   ACIDS  305 

Levo  Tartaric  Acid.  —  Obtained  from  the  inactive  form,  by  splitting 
it  into  its  optical  isomers. 

Racemic  Acid  (inactive).  —  Also  found  in  grapes  and  able  to  be  split 
into  its  active  isomers. 
However,  a  fourth  form  of  tartaric  acid  is  known,  viz., 

Meso-tartaric  Acid.  —  Also  inactive  but  unlike  racemic  acid  it 
cannot  be  split  into  active  isomers. 

It  is  this  fourth  unresolvable  inactive  tartaric  acid  which  gives  to 
tartaric  acid  its  especial  interest  and  importance  in  connection  with 
the  theory  of  stereo-isomerism.  This  acid,  like  the  other  three,  has 
been  fully  explained  in  accordance  with  the  tetra-hedral  theory  of 
van't  Hoff  and  LeBel.  The  explanation  rests  upon  the  fact  that  there 
is  a  second  asymmetric  carbon  atom  in  tartaric  acid.  We  may  construct, 
by  models,  or,  by  drawings,  space-formulas  for  tartaric  acid.  Accord- 
ing to  the  tetra-hedral  theory,  the  dextro,  levo  and  racemic  inactive 
forms  will  be  as  follows,  analogous  to  the  corresponding  formulas  for 
the  three  lactic  acids.  The  meso-tartaric  acid  is  represented  by  the 
third  drawing. 


COOH 


COOH 

OH 


-Tortaric  acid  levo-Tartarix  acid  *  Mwotartaric    acid 

^^^^  (inactive) 


Racemic      acid 

FIG.  6. 

The  dextro  tartaric  acid  has  the  three  groups,  (—COOH),  (—OH), 
( — H)  linked  to  each  of  the  asymmetric  carbons,  arranged  in  a  right 
handed  manner  in  both  of  the  asymmetric  groups.  The  levo  tartaric 
acid  has,  similarly,  a  left  handed  arrangement  in  both  of  the  asymmetric 
groups.  The  racemic  acid  consists  of  equal  molecules  of  these  two  active 
forms  and  is  thus  optically  inactive,  and  is  able  to  be  split  into  its  optically 
20 


306  ORGANIC  CHEMISTRY 

active  components.  The  dextro  and  levo  forms  are  also  enantiomorphs, 
i.e.,  object  and  image  forms,  non-super-imposable.  If,  however,  the 
three  groups,  ( — COOH),  ( — OH),  ( — H),  linked  to  one  asymmetric 
carbon  atom  are  arranged  in  a  right  handed  order  while  those  linked  to  the 
other  asymmetric  carbon  atom  are  in  a  left  handed  order,  as  in  the  third 
drawing  above,  we  would  expect  an  inactive  compound  to  result  in  thai 
one-half  of  the  molecule  would  balance,  or  neutralize  optically,  the 
other  half.  Such  a  compound  can  not  be  split  into  optically  active 
components  without  the  destruction  of  the  molecule.  It  is  termed 
inactive  by  intra-molecular  compensation.  These  ideas  all  agree  with  the 
facts  as  known  in  respect  to  the  four  forms  of  tartaric  acid.  This,  then, 
is  the  extension  of  the  tetra-hedral  theory  of  van't  Hoff  and  Lebel, 
as  applied  to  the  stereo-isomerism  of  tartaric  acid  and  as  has  been  found 
to  apply,  with  equal  fitness,  to  the  case  of  all  compounds  containing 
more  than  one  asymmetric  carbon  atom. 

Historical,  Pasteur. — The  history  of  stereo-isomerism  and  the  tetra- 
hedral  theory  is  so  intimately  connected  with  tartaric  acid  that  it  will 
be  well,  at  this  time,  to  give  a  brief  outline  of  it. 

In  1820  Sir  John  Herschel,  in  considering  the  question  of  the  differ- 
ent optical  rotation  of  crystalline  substances,  suggested  that  it  might 
be  connected  with  an  unsymmetrical  form  of  crystallization.  Later, 
Pasteur  in  1848  while  studying  the  salts  of  tartaric  acid  recalled  this 
suggestion  of  Herschel  and  also  a  statement  by  Mitscherlich  to  the 
effect  that  the  crystalline  form  of  ordinary  tartaric  acid  which  is  dextro 
rotatory  is  identical  with  that  of  racemic  acid  which  is  inactive.  At 
that  time  the  two  tartaric  acids  just  mentioned  were  the  only  ones 
known. 

On  studying  the  sodium-ammonium  salt  of  ordinary  tartaric  acid 
(dextro  tartaric  acid),  to  see  if  there  was  any  indication  of  unsymmetri- 
cal crystalline  form  with  which  to  connect  the  optical  activity,  accord- 
ing to  the  suggestion  of  Herschel,  Pasteur  observed  that  the  crystals 
possessed  hemi-hedral  facets.  These  gave  to  the  crystals  an  unsymme- 
trical form.  He  then  turned  his  attention  to  the  second  known  tartaric 
acid,  viz.,  racemic  acid,  which  is  optically  inactive.  His  expectation 
was  that  in  this  acid  no  such  unsymmetrical  form  would  exist  as  it 
did  not  possess  optical  activity.  But  to  his  surprise  he  found,  in  the 
crystals  of  the  sodium-ammonium  salt,  the  same  hemi-hedral  facets  that 
he  had  just  found  in  the  salts  of  the  active  acid.  On  closer  examination, 


HYDROXY   DI-BASIC   ACIDS  307 

however,  he  observed — and  this  is  the  striking  and  important  thing  in  his 
whole  investigation —  that  the  crystals  were  not  all  alike.  While  some 
possessed  hemi-hedral  facets  on  one  side  others  had  these  facets  on  the 
other  side,  i.e.,  the  two  forms  of  crystals  were,  as  is  termed  in  crystal- 
lography, enantiomorphs,  or,  object  and  image  forms,  like  the  right  hand 
and  the  left.  On  carefully  separating  these  two  forms  of  crystals  he 
found  that  those  of  one  form,  when  dissolved  in  water,  gave  a  solution 
which  rotated  the  plane  of  polarized  light  to  the  right.  In  other  words, 
one  form  of  crystals  was  identical  with  the  salt  of  dextro  tartaric  acid. 
The  crystals  which  showed  the  hemi-hedral  facets  on  the  other  side, 
when  put  into  solution  gave  an  optical  rotation  in  the  opposite  direction, 
i.e.,  to  the  left.  Furthermore,  on  mixing  the  solutions  of  the  two  forms 
of  crystals,  he  obtained  a  solution  that  was  inactive,  like  the  solution 
of  the  original  racemic  acid  salt  with  which  he  started.1 

Thus  from  a  study  of  the  crystalline  sodium-ammonium  salt  of 
racemic  acid  and  of  dextro  tartaric  acid  Pasteur  showed,  conclusively, 
the  relationship  of  these  two  acids  to  each  other  and  also  discovered 
the  existence  of  a  third  isomer  optically  active  but  of  opposite  direction 
to  the  ordinary  tartaric  acid  already  known.  Racemic  acid,  therefore, 
is  optically  inactive  because  it  consists  of  equal  molecules  of  the  ordi- 
nary dextro  tartaric  acid  and  the  newly  discovered  levo  tartaric  acid. 
Also  racemic  acid  can  be  resolved  into  its  optically  isomeric  components 
by  mechanically  separating  the  two  forms  of  crystals  of  the  sodium- 
ammonium  salt.  The  two  active  forms  of  tartaric  acid,  when  mixed 
in  equal  molecular  amounts,  yield  the  inactive  or  racemic  acid.  Later, 
Pasteur  prepared  the  fourth  variety  of  tartaric  acid,  viz.,  meso- 
tartaric  acid,  by  heating  the  cinchonine  salt  of  dextro  tartaric  acid. 
This  new  acid  proved  to  be  inactive  like  racemic  acid,  but,  unlike  it, 
was  unable  to  be  resolved  into  optically  active  components.  Its  relation 
to  the  other  three  forms  of  tartaric  acid  was  unexplained  by  Pasteur. 

In  1873  Wislicenus  made  the  suggestion  that  in  compounds  like 
lactic  acid  and  the  tartaric  acids  in  which  isomers  have  the  same  struc- 
ture but  differ  in  physical  properties,  e.g.,  in  their  rotation  of  polarized 
light,  the  only  explanation  is  that  the  atoms  of  the  molecules  are  differ- 
ently arranged  in  space.  Now,  in  considering  this  suggestion  in  con- 

1  See  Pasteur,  ''Molecular  Asymmetry,"  Alembic  Club  Reprints,  and  Ann.  Ch., 
(3)  28,  56,  1850;  Ann.,  88,  212,  1853;  also,  "Life  of  Louis  Pasteur,"  by  Valery 
Radot. 


308  ORGANIC  CHEMISTRY 

nection  with  the  relation  of  known  optically  active  compounds,  van't 
Hoff  advanced  his  theory  of  the  asymmetric  carbon  atom  and  the  tetra- 
hedral  formula  as  an  explanation  of  the  space  configuration  of  com- 
pounds of  this  nature,  i.e.,  optically  active  like  lactic  acid,  tartaric 
acid,  etc.  At  the  same  time.  LeBel,  in  considering  the  work  of  Pas- 
teur, arrived  at  practically  the  same  idea  though  van't  Hoff  assigned  a 
definite  tetra-hedral  structure  to  the  carbon  atom  in  space,  while  Le- 
Bel simply  assumed  an  unsymmetrical  grouping  of  a  carbon  atom  when 
linked  to  four  different  groups  or  elements.  The  theory  is  thus  known 
as  the  van't  Hoff  -LeBel  theory  of  the  asymmetric  carbon  atom  and  the 
tetra-hedral  configuration.  According  to  this  theory  the  existence  of 
the  fourth  variety  of  tartaric  acid,  viz.,  meso tartaric  acid,  is  fully  ex- 
plained as  inactive  by  intra-molecular  compensation.  The  connection 
of  tartaric  acid  with  the  development  of  our  ideas  of  stereo-chemistry  is 
retained  in  the  application  of  the  term,  racemic,  to  all  compounds 
which,  like  racemic  acid,  are  optically  inactive,  and  resolvable  into  two 
opposite  optically  active  isomers.  Such  an  inactive  form  of  any  com- 
pound is  termed  its  racemic  variety. 

Splitting  Racemic  Compounds. — The  methods  by  which  racemic 
compounds  may  be  split  into  their  optically  active  components  are 
several.  The  three  methods  used  were  all  originated  by  Pasteur.  The 
first  method  has  been  referred  to  and  consists  of  the  mechanical  separa- 
tion of  the  two  oppositely  hemi-hedral  forms  in  which  the  salts  of  a 
racemic  compound  crystallize.  This  method  is  especially  applicable 
in  the  case  of  tartaric  acid  when  the  sodium-ammonium  salt  is  used. 
The  crystallization  and  separation  must  be  carried  out  under  definite 
conditions.  If  the  racemic  acid  salt  is  crystallized  below  28°  the  two 
forms  of  crystals  are  produced  and  a  separation  can  be  accomplished. 
If,  however,  the  crystallization  takes  place  above  28°  the  two  forms  of 
crystals  are  not  produced  but  the  sodium-ammonium  racemate  crys- 
tallizes in  unseparable  crystals  of  one  form.  That  is,  above  28°  the 
sodium-ammonium  racemate  crystallizes  as  such,  while,  below  28°  the 
racemate  splits  into  its  two  isomeric  components  and  equal  amouts  of 
the  sodium-ammonium  dextro  tartrate  and  the  sodium-ammonium 
levo  tartrate  are  formed.  The  second  method  for  the  splitting  of  a 
racemic  compound  into  its  optically  active  components  consists  of  the 
formation  of  the  cinchonine,  strychnine,  or  other  similar  alkaloid  salts. 
When  the  cinchonine  salt  of  racemic  acid  is  formed  it  splits  into  the 


HYDROXY   DI-BASIC   ACIDS  309 

cinchonine  salts  of  dextro  and  levo  tartaric  acid.  These  two  salts  do 
not  crystallize  in  different  forms  which  permit  their  mechanical  sepa- 
ration, but  they  crystallize  at  different  concentrations.  The  salt  of 
the  levo  tartaric  acid  crystallizes  out  first  and  may  be  separated. 
Afterward  the  salt  of  the  dextro  tartaric  acid  crystallizes  and  may  then 
be  obtained  by  itself.  Thus  by  a  fractional  crystallization  of  the  alka- 
loid salts  of  racemic  compounds  they  may  be  separated  into  their  optic- 
ally active  components.  The  third  method  for  the  splitting  of  racemic 
compounds  is  known  as  the  biological  method.  It  rests  upon  the  rela- 
tion of  the  different  acids  or  salts  to  certain  lower  organisms,  especially 
the  molds.  When  the  mold,  Penicillium  glaucum,  is  grown  in  a  solu- 
tion of  ammonium  racemate,  or  some  other  racemic  salt,  it  uses  as 
nutritive  material  the  ammonium  dextro  tartrate  which  becomes, 
therefore,  destroyed  and  removed  from  the  solution.  The  ammonium 
salt  of  the  levo  tartrate  is,  however,  not  used  by  the  organism  and  re- 
mains in  the  solution.  After  the  action  the  solution  yields,  on  crystal- 
lization, crystals  of  the  levo  tartrate  only.  Thus  by  the  destruction 
and  removal  from  the  solution  of.  the  racemate  of  one  of  the  optically 
active  components,  by  means  of  molds,  the  other  isomer  is  obtained 
in  the  pure  form. 

Dextro  Tartaric  Acid 

Dextro  tartaric  acid  is  the  ordinary  tartaric  acid  as  it  is  found  widely 
distributed  in  nature,  in  grapes,  mountain  ash  berries,  pineapples, 
potatoes  and  other  plants.  It  crystallizes  without  water  of  crystalli- 
zation in  transparent,  mono-clinic  columns  which  are  easily  soluble  in 
water  or  in  alcohol.  100  parts  of  water  at  15°  dissolve  132  parts  of 
the  acid.  It  melts  at  i68°-i7O°.  In  water  solution  it  is  dextro  rota- 
tory. The  chief  source  of  tartaric  acid  is  the  juice  of  the  grape,  where 
it  is  present  as  the  free  acid  and  as  the  acid  potassium  salt.  In  this 
source  it  is  mostly  the  dextro  variety  that  is  found.  It  is  obtained  from 
the  vinasse,  or  residue  which  settles  out  from  the  juice  after  it  has  been 
expressed.  When  grape  juice  ferments,  in  the  formation  of  wine,  the 
solubility  of  the  acid  potassium  salt  is  lessened  due  to  the  presence  of 
alcohol  and  it  gradually  separates  and  settles  to  the  bottom  in  the  form 
of  what  is  known  as  lees.  These  lees  are  dried  or  recrystallized  once 
and  the  product  is  then  known  as  crude  tartar  or  argol.  The  crude 
tartar  contains,  in  addition  to  the  acid  potassium  tartrate,  free  tartaric 


310  ORGANIC  CHEMISTRY 

acid  and  calcium  tartrate.  By  recrystallization  and  purification  the 
pure  acid  potassium  tartrate  is  obtained.  In  the  pure  form  this  salt 
is  known  as  cream  of  tartar.  The  English  name  of  the  acid  is  derived 
from  its  relation  to  this  tartar,  i.e.,  tartaric  acid.  The  German  name 
of  the  acid,  viz.,  Wein-saure,  is  derived  from  the  fact  that  it  separates 
out  when  wine  is  formed.  The  free  dextro  tartaric  acid  is  obtained 
from  either  the  crude  or  the  pure  tartar  by  first  treating  with  milk  of 
lime  and  subsequently  with  calcium  sulphate.  This  forms  the  cal- 
cium salt  which  is  then  decomposed  by  means  of  sulphuric  acid  and 
the  tartaric  acid  set  free.  This  is  then  recrystallized  and  obtained  in 
the  pure  form. 

The  synthetic  transformation  of  dextro  tartaric  acid  into  malic, 
succinic  and  maleic  acids  has  already  been  spoken  of.  When  heated 
to  its  melting  point  dextro  tartaric  acid  is  converted  into  meso-tartaric 
acid.  This  conversion  also  takes  place  when  a  solution  of  dextro 
tartaric  acid  is  evaporated.  When  it  is  heated  with  water  to  175° 
dextro  tartaric  acid  yields  both  racemic  acid  and  meso-tartaric  acid. 
Long  heating  with  hydrochloric  acid  yields  racemic,  meso-tartaric  and 
pyro-tartaric,  (methyl  succinic)  acids.  By  distillation  it  yields  pyro- 
tartaric  acid  and  other  acids.  Tartaric  acid  reduces  ammoniacal 
silver  solution  and  can  be  used  for  silvering  purposes.  In  this  reaction 
the  tartaric  acid  is  oxidized  to  oxalic  and  other  acids.  When  tartaric 
acid,  or  a  salt,  is  heated  a  characteristic  odor  of  burnt  sugar  is  observed. 
The  free  acid  is  used  as  a  cheaper  substitute  for  citric  acid  in  beverages. 
It  is  also  used  as  a  mordant  in  dyeing,  and  in  medicine  and  photography. 

Salts. — Several  of  the  salts  of  dextro  tartaric  acid  are  important. 

CH(OH)— COOK 
Acid  Potassium  Tartrate.     | 

CH(OH)— COOH 

This  salt  has  already  been  referred  to  as  cream  of  tartar.  It  forms 
rhombic  crystals  which  are  only  slightly  soluble  in  water.  One  of  its 
important  uses  is  as  a  constituent  of  baking  powders.  In  such  powders 
the  other  constituent  is  sodium  acid  carbonate.  It  is  also  used  as  a 
mordant  in  dyeing. 

CH(OH)— COONa 

Sodium-potassium  Tartrate,      |  +  4H2O 

Rochelle  Salt.  CH(OH)— COOK 


HYDROXY   DI-BASIC   ACIDS  311 

This  salt  crystallizes  in  thick  columns  with  four  molecules  of  water. 
Its  chief  use  is  as  a  reducing  agent.  It  reduces  an  ammoniacal  silver 
solution  and  in  this  way  is  used  in  silvering  glass.  It  is  also  used  as  a 
constituent  of  Fehling's  solution,  (p.  332),  which  is  an  alkaline  copper 
solution  reduced  by  certain  sugars.  It  acts  as  a  purgative  in  Seidlitz 
powders  which  consist  of  sodium-potassium  tartrate,  sodium  acid 
carbonate  and  free  tartaric  acid. 

CH(OH)— COOK 
Potassium -antimonyl  Tartrate. 

Tartar  Emetic.  CH(OH)— COO(SbO) 

This  salt  is  used  in  medicine  as  an  emetic. .   It  is  also  used  in  dyeing. 

Levo  Tartaric  Acid 

Levo  tartaric  acid,  the  optical  isomer  of  dextro  tartaric  acid,  was 
discovered,  as  already  stated,  by  Pasteur  in  1848.  It  has  the  same 
solubility  and  melting  point  as  the  dextro  acid.  It  crystallizes  without 
water  of  crystallization  in  the  form  enantiomorphic  to  the  dextro  acid. 
Its  optical  rotation  is  the  same  in  amount  but  opposite  in  direction  to 
the  dextro  acid.  When  mixed  in  equal  molecular  amount  with  dextro 
tartaric  acid  it  yields  racemic  acid.  Its  synthetic  reactions  have  been 
considered.  It  has  no  common  uses. 

Racemic  Acid 

Racemic  acid,  the  resolvable  inactive  tartaric  acid,  was  discovered  in 
1820  and  was  shown  to  be  tartaric  acid  in  1830.  It  crystallizes  in 
tri-clinic  needles  containing  one  molecule  of  water,  per  unit  molecule 
of  C4H6O4.  In  this  it  differs  from  the  dextro  and  levo  forms.  The 
water  free  acid  melts  at  2O5°-2o6°,  the  hydrous  crystals  melting  at 
2O3°-2O4°.  At  15°  100  parts  of  water  dissolve  17  parts  of  the  acid,  it 
being  less  soluble  than  the  active  forms.  While,  in  concentrated 
solution  the  acid  exists  as  a  double  molecule,  the  crystals  which  separate 
being  those  of  racemic  acid,  in  dilute  solution  the  acid  exists  as  equal 
molecular  parts  of  dextro  and  levo  tartaric  acid.  These  facts  are 
shown  by  the  results  of  freezing  point  determinations.  Racemic  acid  is 
found,  together  with  dextro  tartaric  acid,  in  grapes.  Its  English 
name  is  derived  from  raceme,  indicating  a  bunch  of  grapes.  The 


312  ORGANIC  CHEMISTRY 

German  name,  Trauben-saure,  is  derived  from  the  word  for  grapes. 
It  is  probable  that  it  does  not  exist  in  grapes  as  racemic  acid  but  that 
it  is  formed  from  the  dextro  acid  as  this  transformation  can  easily  be 
effected  by  the  action  of  acids  or  even  by  water  alone.  When  tartaric 
acid  is  prepared  synthetically  from  succinic  acid,  from  glyoxal,  or  from 
malic,  maleic  or  fumaric  acids  either  racemic  acid  or  meso-tartaric  acid 
is  always  formed.  That  is,  synthetic  reactions  result  in  the  formation 
of  an  inactive  form.  The  methods  of  splitting  racemic  acid  into  its 
optically  active  components  has  been  fully  discussed.  The  sodium- 
ammonium  racemate  is  the  only  salt  that  is  of  importance.  This  has 
been  spoken  of  in  connection  with  the  method  of  splitting  racemic 
acid  into  its  components.  Like  the  free  acid  this  salt  exists,  in  dilute 
solution,  as  equal  molecular  parts  of  the  dextro  and  levo  forms.  Only 
in  concentrated  solution  does  it  exist  as  the  racemate  itself. 

Meso-tartaric  Acid 

This  acid,  the  inactive  by  mtra-molecular  compensation  and  un- 
resolvable  into  optically  active  components,  was  first  obtained  by 
Pasteur  by  heating  the  cinchonine  salt  of  dextro  tartaric  acid,  to  170°. 
It  may  also  be  prepared  by  boiling  the  dextro  tartaric  acid  with  an 
excess  of  hydrochloric  acid,  or  with  sodium  hydroxide.  Also  by  long 
boiling  with  water  alone  or  by  heating  with  a  small  amount  of  water 
to  165°.  When  di-brom  succinic  acid  is  treated  with  silver  hydroxide, 
or  when  malic  acid  is  oxidized,  in  the  presence  of  water,  both  meso- 
tartaric  acid  and  racemic  acid  are  formed.  When  meso-tartaric  acid 
is  heated  to  200°  it  is  partly  converted  into  racemic  acid.  Meso- 
tartaric  acid  crystallizes  in  rectangular  plates  with  one  molecule  of 
water.  The  water  free  acid  melts  at  i4O°-i45°. 

IV.  TRI-BASIC  ACIDS  AND  HYDROXY  TRI-BASIC  ACIDS 
Tri-carballylic  Acid  and  Aconitic  Acid 

Tri-basic,  tetra-basic  and  penta-basic  acids  are  known  but  most  of 
them  are  not  of  sufficient  importance  to  consider  at  any  length.  We 
shall  simply  mention  and  give  the  formulas  for  two  members  of  the 
first  group.  Two  tri-basic  acids  are  found  in  the  juice  of  sugar  cane  or 
in  the  residue  which  settles  out  when  the  sugar  cane  juice  is  evaporated. 
The  two  acids  are  both  related  to  citric  acid  which  we  shall  consider 
next.  They  are  known  as  tri-carballylic  acid  and  as  aconitic  acid. 


CITRIC    ACID 


313 


The  first  has  been  proven  to  have  the  constitution  of  i-2-$-tri-carboxy 
propane  and  the  second  is  the  unsaturated  double  bond  acid  derived 
from  the  first.  The  formulas  are  as  follows: 


CH2— COOH 


CH— COOH 


Tri-carballylic  acid  CH— COOH  C— COOH 


CH2— COOH          CH2— COOH 


Aconitic  acid 


The  two  acids  may  be  converted  into  each  other  by  the  appropriate 
reactions  for  passing  from  saturated  to  unsaturated  compounds,  or 
the  reverse. 

Citric  Acid 

Synthesis  from  Glycerol.  —  Citric  acid  is  related  to  the  two  preceding 
acids  and  its  constitution  has  been  established  by  two  syntheses,  one 
from  glycerol  and  the  other  from  aceto-acetic  ester. 


CH2— OH 
CH— OH 
CH2— OH 

Glycerol 

CH2— Cl 


CH2—  Cl 


CH2— Cl 


HC1 


+  O 


CH  —OH 


C  =  O 


CH2— Cl 

+HCN  |     ,OH 
i/ 


H20 


CH2— Cl 

Sym.  di-chlor 
hydrine 


CH2— Cl 


Sym.  di-chlor 
acetone 


+  KCN 


I  ^COOH 
CH2— Cl 

Di-chlor 

hydroxy 

iso-butyric 

acid 


CH2— CN 
!/OH 

I^COOH 
CH2— CN 

Nitnle 
of  citric  acid 


+  H20 


^CN 
CH2— Cl 

HCN— add. 
product 

CH2— COOH 
|XOH 
CX 


CH2— COOH 

Citric  acid 


The  glycerol  is  converted  into  the  symmetrical,  or,  I  -3  -di-chlor -hydrine. 
By  oxidation  this  yields  the  symmetrical,  or,  1-3 -di-chlor  acetone, 
which  by  the  addition  of  hydrogen  cyanide  yields  the  addition  product, 
that  on  hydrolysis  is  converted  into  a  hydroxy  acid,  viz.,  di-chlor 
hydroxy  iso-butyric  acid.  By  treatment  with  potassium  cyanide  this 
yields  the  corresponding  di-cyanide,  or  nitrile  of  citric  acid  which  on 
hydrolysis  yields  citric  acid. 


ORGANIC  CHEMISTEY 


From  Aceto-Acetic  Ester. — The  synthesis  from  aceto-acetic  ester 
takes  place  according  to  the  following  scheme : 

CH3  CH2— Cl  CH2— CN 


C  =  O 


O 


C  =  O 


CH2— COOC2H5 

Aceto-acetic  ester. 


CH2— COOC2H5 

Chlor  aceto-acetic 
ester 


CH2— COOC2H5 

Cyan  aceto-acetic 


CH2— COOC2H5 


O 


CH2— COOC2H5 

Acetone  di-carbozylic 
acid  ester 


ester 

CH2—  COOC2H5 
X 


|      CN 
CH2—  €OOC2H5 

Addition  product 


CH2— COOH 
/OH 

|  XCOOH 
CH2— COOH 

Citric  acid 


These  syntheses  establish  the  constitution  of  citric  as  a  2-hydroxy 
1-2-3  tri-carboxy  propane,  i.e.,  it  is  a  tri-basic  mono-alcoholic  acid. 

Citric  acid  is  one  of  the  most  important  plant  acids  and  is  widely 
distributed  in  various  parts  of  many  plants.  It  is  found  free,  especially 
in  citrus  fruits  (lemons,  limes,  etc.),  and  associated  with  malic  and 
tartaric  acid  in  currants,  goose-berries,  raspberries,  mountain  ash  berries, 
etc.  It  is  also  found  as  the  calcium  salt  in  cow's  milk  and  in  grape  twigs. 
The  chief  commercial  source  is  the  lemon,  where  it  is  present,  in  the 
unripe  lemon,  to  about  5  per  cent.  It  is  formed  when  glucose  sugar  is 
fermented  with  a  particular  mold,  Citromyces  citricus.  The  chief 
uses  of  the  acid  are  as  a  constituent  of  lemonade  and  other  beverages, 
and  in  the  printing  of  calico  prints.  It  crystallizes  in  rhombic  prisms 
which  contain  one  molecule  of  water.  The  water  is  lost  by  heating  to 
130°  and  the  water  free  acid  melts  at  153°.  From  cold  water  the  acid 
crystallizes  in  water  free  crystals.  It  is  readily  soluble  in  water.  When 
heated  to  175°  it  loses  water  and  is  converted  into  the  unsaturated  acid, 
aconitic,  which  by  reduction  yields  the  corresponding  saturated  acid, 
viz.,  tri-carballylic  acid. 


CH2— COOH 
,OH 


\:OOH 

CH2— COOH 

Citric  acid 


-  H2O 


CH— COOH 


C—  COOH 


CH2— COOH 

Aconitic  acid 


H 


CH2— COOH 
CH— COOH 
CH2— COOH 

Tri-carballylic  acid 


CITRIC  ACID  315 

These  reactions  show  the  relation  of  citric  acid  to  the  two  tri-basic 
acids  mentioned  at  the  beginning  of  this  section.  When  subjected  to 
dry  distillation  citric  acid  loses  carbon  dioxide  while  at  the  same  time 
it  becomes  oxidized,  and  acetone  is  produced. 

CH2— COOH  CH3  CH3 

|    ,OR          -  3C02  ,OH      +  O         | 

c(  c(  c  =  o 

XCOOH  |  XH  | 

CH2— COOH  CH3  CH3 

Citric  acid  Acetone 

In  the  decomposition  by  heat  other  acids  are  also  formed,  viz., 
ita-conic  and  citra-conic  acids  (p.  293).  In  this  case  both  carbon 
di-oxide  and  water  are  lost, 

CH2— COOH  CH3  CH2 

OH  -CO2  |  || 

-*  C— COOH     and  C— COOH 

COOH  — H20  ||  | 

CH2— COOH  CH— COOH  CH2— COOH 

Citric  acid  Citra-conic  acid  Ita-conic  acid 

»      r*-') 
All  of  the  syntheses  and  decompositions  of  citric  acid  prove  its 

constitution  to  be  as  represented. 

Salts. — As  citric  acid  is  a  tri-basic  acid  it  forms  three  series  of  salts, 
e.g.,  with  sodium  it  yields  the  mono-,  di-  and  tri-sodium  salts,  the  last 
being  the  neutral  sodium  citrate.  Only  three  salts  of  citric  acid  are 
of  importance. 

Neutral  Ammonium  Citrate. — A  solution  of  this  salt  is  used  in  the 
analysis  of  fertilizers  to  represent  the  solvent  action  of  plant  juices 
and  soil  water. 

Magnesium  Citrate. — This  salt  is  used  in  medicine  as  a  purgative. 
Mixed  with  sodium  bi-carbonate,  free  citric  acid  and  sugar  it  produces 
a  pleasant  effervescing  purgative. 

Ferric  Ammonium  Citrate.— This  salt,  a  soluble  salt  of  iron  and 
ammonia,  is  used  in  calico  printing  and  in  the  blue-print  photographic 
process. 

Ferric  Citrate. — The  single  iron  salt  of  citric  acid  forms  colloidal 
solutions  and  is  used  in  the  study  of  colloids. 


316  ORGANIC  CHEMIS1EY 


X.  CARBOHYDRATES 
GENERAL 

Oxidation  Products  of  Poly-hydroxy  Alcohols. — In  our  study  of 
the  mixed  poly-substitution  products  we  considered  the  mixed  alcohol- 
aldehyde  and  alcohol-ketone  compounds  and  showed  that  they  are 
intermediate  oxidation  products  between  poly-hydroxy  alcohols  and 
poly-basic  acids  (p.  228).  To  illustrate,  when  glycerol,  tri-hydroxy 
propane,  is  oxidized  the  following  products  are  obtained. 

CH2— OH  CHO  CH2— OH 

CH— OH       +  O  — »        CH— OH     and     C  =  O 

CH2— OH  CH2— OH  CH2— OH 

Glycerol  Glyceric  aldehyde  Di-hydroxy  acetone 

The  formation  of  the  two  products  depends  upon  the  fact  that  in 
one  case,  di-hydroxy  acetone,  the  secondary  alcohol  group  of  the  glycerol 
is  oxidized  to  a  ketone  group  while  in  the  other  case,  glyceric  aldehyde, 
one  of  the  primary  alcohol  groups  is  oxidized  to  an  aldehyde  group. 
The  reason  for  waiting  until  this  time  for  the  full  consideration  of  these 
alcohol-aldehyde  and  alcohol-ketone  compounds  is,  that  these  com-t 
pounds  and  their  derivatives  constitute  that  most  important  group 
known  as  the  carbohydrates,  or  sugars,  including  such  well  known  sub- 
stances as  glucose  sugar,  cane  sugar,  starch  and  cellulose.  Because 
of  relationships  between  them  and  the  di-basic  acids  and  also  because 
of  their  relation  to  stereo-isomerisms  which  we  have  developed  more 
fully  in  connection  with  lactic  and  tartaric  acids,  it  was  best  not  to 
take  up  the  carbohydrates  until  after  the  poly-basic  acids  and  the 
hydroxy  acids  had  been  studied.  We  shall  first  consider  the  composi- 
tion and  constitution  of  the  carbohydrates  wholly  independent  of  the 
historical  development  of  the  facts  or  of  the  natural  classification  of 
the  different  members  of  the  group. 

Composition  and  Constitution. — The  name  saccharoses  applies  in 
general  to  all  carbohydrates  and  the  termination  ose  is  used  in  the 
names  of  most  of  the  different  groups  and  individuals.  Whenever 


CARBOHYDRATES  317 

used  this  termination  always  means  a  carbohydrate.  The  name  sac- 
charide  is  often  used  but  the  termination  ose  is  much  to  be  preferred. 
The  more  important  carbohydrates  have  the  composition  represented 
by  the  following  general  formulas,  which  apply  in  all  cases  except 
in  those  of  methyl  derivatives  and  the  group  of  tri-saccharoses. 

CnH2nOn  or  Cn(H2O)n  e.g.         C6H12O6 

CnH2n_2On_r  or  Cn(H2O)n_r  e.g.         Ci2H22On 

(CnH2n_2On_:)x         or          (CnCHjOn-Jx       e.g.        (C6H10O5)X 


That  is,  carbohydrates,  so  far  as  their  empirical  composition  is 
concerned,  are  carbon-water  compounds.  This  explains  the  origin 
of  the  name  carbo-hydrates,  i.e.,  carbon-water  compounds.  This  idea 
that  carbohydrates  were  carbon-water  compounds  was  supported  by 
the  fact  that  on  heating  or  on  treatment  with  a  dehydrating  agent, 
like  sulphuric  acid,  the  compounds  were  decomposed  into  water  and 
carbon.  This  may  easily  be  shown  by  simple  experiments.  On 
heating  sugar  in  a  dry  test  tube  it  gradually  chars  and  gives  off  water 
until  only  carbon  is  left.  Also,  when  dry  sugar  is  treated  with  sulphuric 
acid  it  chars  in  a  like  manner  and  a  residue  of  pure  carbon  remains. 
The  simplest  group,  with  the  general  formula  CnH2nOn,  embraces  sub- 
groups which  contain  different  amounts  of  carbon  varying  from  three  to 
nine  atoms  to  the  molecule.  They  are  termed  simple  carbohydrates, 
simple  sugars  or  mono-saccharoses  and  the  names  of  the  sub-groups 
are  made  from  the  termination  ose,  together  with  the  numerical  prefix 
indicating  the  number  of  carbon  atoms  present.  We  have,  therefore, 
as  follows: 

Simple  Carbohydrates,     CnH2nOn 
Mono-saccharoses 

Tri-oses,  C3H6O3 

Tetroses,  C4H8O4 

Pent  oses,  CsHioOs 

Hexoses,  CeH^Oe 

Heptoses,  C7Hi4O7 

Octoses,  C8Hi6O8 

Nonoses,  C9Hi8O9 

It  is  necessary  to  state  this  much  in  regard  to  the  simple  sugars,  be- 
fore taking  them  up  in  detail,  because,  in  developing  our  ideas  of  con- 


318  ORGANIC  CHEMISTRY 

stitution  and  in  studying  the  general  reactions  of  the  carbohydrates 
as  a  whole,  we  must  use  some  of  these  compounds  as  illustrations. 

The  relation  between  carbon,  hydrogen  and  oxygen  in  the  composi- 
tion of  the  carbohydrates  shows  nothing,  however,  as  to  the  constitution 
of  the  compounds  except  that  it  indicates  the  probable  presence  of 
secondary  alcohol  groups,  (  =  CH(OH)),  which,  it  will  be  observed,  have 
the  same  relative  amounts  of  the  three  elements  in  question.  It  is 
impossible  to  conceive,  however,  of  a  compound  as  built  up  of  secondary 
alcohol  groups  only. 

Alcohol  Compounds. — That  the  carbohydrates  are,  in  fact,  alcohol 
compounds  is  shown,  both  by  their  relation  to  poly-hydroxy  alcohols 
and  by  their  reactions.  Carbohydrates  possess  alcohol  characters  in 
that  they  undergo  distinctly  alcoholic  reactions.  Like  all  alcohols 
they  react  with  acetyl  chloride  or  acetic  anhydride.  In. practice  the 
latter  reagent  is  used.  They  form  acetyl  derivatives,  or  esters,  just  as 
ethyl  alcohol  does. 

C2H5— OH  +  C1OC— CH3        >        C2H5— OOC— CH3  +  HC1 

Ethyl  alcohol  Ethyl  acetate 

CHO  CHO 

CH— OH     +     Cl— OC— CH3         — >      CH— OOC— CH3  +  2HC1 

CH2— OH  CH2— OOC— CH3 

Glyceric  aldehyde  Di-acetyl  glyceric  aldehyde 

Glycerose  (a  triose). 

Esterification  or  Acetylation. — This  reaction  is  of  especial  im- 
portance, because  it  not  only  proves  the  presence  of  hydroxyl  groups, 
but,  it  determines  their  number,  for  complete  acetylation  introduces 
as  many  acetyl  groups  as  there  are  hydroxyl  groups  in  the  original  com- 
pound. 

Number  of  Hydroxyl  Groups. — In  this  way  it  has  been  shown  that 
in  the  simple  carbohydrates  the  number  of  hydroxyl  groups  is  one  less 
than  the  number  of  carbon  atoms.  As  more  than  one  hydroxyl  group  is 
not  usually  linked  to  one  carbon  the  indication  is  that  each  carbon 
atom  but  one  has  one  hydroxyl  group  linked  to  it.  That  the  remaining 
carbon  atom  is  in  a  carbonyl  grouping  was  first  established  by  Kiliani, 
who  showed  that  in  water  solution  the  carbohydrates  are  aldehyde  or 
ketone  compounds  as  well  as  poly-hydroxy  alcohols. 


CARBOHYDRATES 


319 


Aldehyde  or  Ketone  Compounds. — This  aldehyde  or  ketone  con- 
stitution is  proven  by  several  reactions. 

Aldehyde  and  Ketone  Reactions. — (i)  The  formation  of  addition 
products  with  hydrogen  cyanide,  H — CN.  (2)  The  formation  of 
oxime  compounds  with  hydroxyl  amine,  H2 — NOH.  (3)  The  forma- 
tion of  hydra-zone  compounds  with  a  benzene  compound  known  as 
phenyl  hydrazine,  H2N— NH— C6H5. 

These  three  reactions  are  all  characteristic  of  compounds  which 
contain  the  carbonyl  group,  i.e.,  aldehydes  or  ketones  (p.  125).  They 
may  be  illustrated  as  follows: 


H 

Aldehydes  R— C  =  0+H— CN 

R 
Ketones      R— C=0+H—  CN 

H 

I 
Aldehydes  R— C  =  O+H2N— OH 

R 

Ketones      R— C  =  O+H2N— OH 
H 


H 

>R— C— OH 

I 
CN      Cyan-hydrines. 

(Nitriles  of 
R        hydroxy  acids.) 

»R— C— OH 

CN 
H 

»R— C  =  N— OH 

R 

I 
>R— C  =  N— OH 

H 


Oximes. 


Aldehydes  R— C  =  O+H2N— NH— C6H5 »R— C  =  N— NH— C6H6 

Phenyl 
R  R  hydrazones. 


Ketones      R— C  =  O+H2N— NH— C6H5 >R— C  =  N— NH— C6H, 


320  ORGANIC  CHEMISTRY 

All  of  these  reactions  as  given  above  for  aldehydes  and  ketones  in 
general,  take  place  with  the  simple  carbohydrates  when  they  are  in 
solution  in  water  and  constitute  the  chief  proof  that  in  such  solution 
they  are  aldehyde  or  ketone  compounds. 

Synthesis. — The  carbohydrates  have  been  prepared  synthetically 
by  oxidizing  the  poly-hydroxy  alcohols.  We  have  recently  spoken 
of  the  mixed  alcohol  and  aldehyde  or  mixed  alcohol  and  ketone  com- 
pounds which  are  formed  by  the  oxidation  of  the  tri-hydroxy  alcohol 
glycerol.  We  have,  also,  just  stated  that  the  carbohydrates  have 
been  proven  to  be  mixed  poly-hydroxy  alcohols  and  aldehydes  or 
ketones.  The  compound  just  referred  to,  as  produced  by  the  oxida- 
tion of  glycerol,  is  the  simplest  compound  which  has  the  character  of  a 
true  sugar.  Its  composition  is  in  accordance  with  the  first  of  the 
general  formulas,  viz.,  C3H603  or  CnH2nOn,  and  from  the  number  of 
carbon  atoms  present  it  would  be  termed  a  triose.  The  oxidation  of 
glycerol  results  in  a  mixture  of  two  compounds,  viz.,  an  aldehyde 
alcohol  and  a  ketone  alcohol. 

CH2— OH  CHO  CH2— OH 

I  I  I 

CH— OH         +    O     >        CH— OH      and      C  =  O 

CH2— OH  CH2— OH  CH2— OH 

Glycerol  Glyceric  aldehyde  Di-hydroxy  acetone 

Glycerose. — Glycerose,  C3H603,  a  triose,  is  a  mixture  of  these  two 
definite  compounds,  glyceric  aldehyde  and  di-hydroxy  acetone.  It  is 
the  simplest  carbohydrate  possessing  the  general  character  of  a  sugar. 
It  was  discovered  by  Deen  in  1863 .  It  reacts  with  acetic  anhydride,  form- 
ing acetyl  derivatives  in  which  the  alcoholic  hydroxyls  are  the  reacting 
groups.  It  also  reacts  with  hydrogen  cyanide,  forming  addition  prod- 
ucts, cyan-hydrines,  with  the  aldehyde  or  ketone  groups.  The  alde- 
hyde or  ketone  groups  also  react  with  phenyl  hydrazine  forming  hydra- 
zones  and  with  hydroxyl  amine  yielding  oximes.  Glycerose,  as  it  has 
been  obtained,  is  not  a  single  compound  but  a  mixture  of  two,  one  being 
an  aldehyde  and  the  other  a  ketone.  It  seems  probable  that  either  of 
these  compounds  alone  is  a  true  carbohydrate  but  at  present  we  know 
this  simplest  sugar  only  as  a  mixture  of  the  two.  In  the  case  of  the 
higher  members  of  the  simple  carbohydrates  containing  four  to  nine 


CARBOHYDRATES  321 

carbons,  we  find  in  each  two  distinct  compounds,  just  as  in  glycerose, 
but  in  all  cases  except  glycerose,  each  compound,  by  itself,  is  a 
true  carbohydrate  and  is  also  a  true  sugar  in  its  general  properties  such 
as  taste.  Thus  we  have  two  different  kinds  of  simple  sugars,  viz., 
aldehyde  sugars  and  ketone  sugars.  To  distinguish  between  these  and 
to  retain  the  termination  ose  for  all  carbohydrates,  the  terms  aldose 
and  ketose  are  used.  Thus  while  the  triose  sugar  is  known  only  as  a 
mixed  aldose  and  ketose  each  of  the  other  simple  sugar  groups,  viz., 
tetroses,  pentoses,  hexoses,  heptoses,  octoses  and  nonoses  are  known  both 
as  an  aldose  and  ketose.  The  six  carbon  sugars,  hexoses,  which  are 
our  most  common  and  important  sugars,  are  thus  known  as  two  dis- 
tinctly different  compounds.  One  is  an  aldehyde  sugar  or  aldose,  while 
the  other  is  a  ketone  sugar  or  ketose.  We  therefore  also  term  the 
first  an  aldo-hexose  and  the  second  a  keto-hexose.  The  two  compounds 
are  structural  isomers  both  having  the  composition  formula  CeH^Oe. 
We  shall  consider  them  in  detail  later  on.  The  first,  the  aldo-hexose, 
is  known  as  glucose  and  the  keto-hexose  as  fructose.  The  reverse  of  the 
preceding  reaction  also  establishes  the  constitution  of  the  carbohy- 
drates. 

Reduction. — By  reduction  they  are  converted  into  the  poly-hydroxy 
alcohols  containing  the  same  number  of  carbon  atoms. 

CHO  CH2— OH  CH2— OH 

CH— OH    +    H       — >        CH— OH        <-       H    +    C  =  O 
CH2— OH  CH2— OH  CH2— OH  ' 

Aldo-triose  Glycerol  Keto-triose 

Propan-tri-ol 

Straight  Chain  Compounds. — The  poly-hydroxy  alcohols,  thus  ob- 
tained from  the  carbohydrates,  may  be  further  reduced,  by  means  of 
hydrogen  iodide,  first  to  the  iodine  substitution  product  of  the  corre- 
sponding hydrocarbon  and  then  to  the  hydrocarbon  itself.  Thus,  we 
may  pass  from  the  carbohydrate  to  the  hydrocarbon  corresponding  to 
it  and  containing  the  same  number  of  carbon  atoms.  From  glycerose, 
through  glycerol,  according  to  the  above  reactions,  we  may  obtain 
iodo  propane  and  then  propane.  The  important  fact  is  that  we  ob- 
tain, in  every  case,  the  normal  hydrocarbon.  This  means  that  the  struc- 
ture of  the  carbohydrates  is  that  of  a  normal  chain  of  carbon  groups. 
21 


322  ORGANIC  CHEMISTRY 

This  may  be  best  illustrated  by  taking  glucose  the  aldo-hexose,  the 
exact  constitution  of  which  we  shall  develop  later, 

CH2OH— (CHOH)4— CHO  >  CH2OH— (CHOH)4— CH2OH 

Aldo-hexose  Hexan-hex-ol 

Glucose  Mannitol 

>     CH3— CH2— CH2— CHI— CH2— CH3 

3-Iodo  hexane 
Normal  lodo  hexane 

Position  of  Aldehyde  Group. — If,  then,  the  carbohydrates  are  com- 
pounds made  up  of  a  normal  chain  of  carbon  groups,  each  carbon  group 
but  one  containing  one  and  only  one  hydroxyl,  and  the  remaining  carbon 
group  is  a  carbonyl  group  (aldehyde  or  ketone),  it  remains  simply  to 
determine  the  position  of  this  carbonyl  group.  The  character  of  the 
hydroxyl  grouping,  i.e.,  whether  as  primary  alcohol  or  as  secondary 
alcohol,  is  determined  simply  by  the  fact  that  the  end  carbons,  in  normal 
carbon  chains,  if  containing  a  hydroxyl  group,  must  always  be  a  pri- 
mary alcohol  group,  and  the  intermediate  carbons,  in  the  same  kind  of 
chain,  must  be  secondary  alcohol  groups.  Therefore,  the  end  carbon 
groups  are  the  only  ones  possible  of  existence  as  an  aldehyde  group  and 
the  aldehyde  group,  in  aldoses,  must  be  the  end  carbon  group.  Taking, 
therefore,  the  aldo-hexose  glucose  as  an  example,  we  should  write  the 
formula  as  follows: 

C6Hi2O6  =  CH2OH— CHOH— CHOH— CHOH— CHOH— CHO 

Aldo-hexose,  Glucose 

We  have,  however,  another  proof  that  the  aldehyde  group  is  the 
end  group  of  the  carbon  chain.  By  the  addition  of  hydrogen  cyanide, 
a  reaction  characteristic  of  the  carbonyl  group,  as  previously  discussed, 
we  obtain  from  the  aldo-hexose  a  cyan-hydrine  and  this  cyan-hydrine, 
like  all  cyanogen  compounds,  is  an  acid  nitrile,  which  yields,  on  hydroly- 
sis, an  acid  which  contains,  not  six  carbons  as  the  aldo-hexose  did,  but 
seven  carbons.  That  is,  we  have  increased  the  number  of  carbons  by  one. 
Furthermore,  the  acid  so  obtained  is  the  normal  acid,  viz.,  normal 
heptanoic  acid,  CH3— (CH2)5— COOH.  We  do  not  get  the  normal 
heptanoic  acid,  at  once,  as  the  result  of  the  hydrolysis  but  thelactoneof 
hexa-hydroxy  heptanoic  acid,  CH2OH— (CHOH)  5— COOH,  which  by 
reduction  gives  us  the  non-hydroxy  normal  acid. 

CH2OH— CHOH— CHOH— CHOH— CHOH— CHO  +  HCN 

Glucose 


CARBOHYDRATES  323 

H 

I 
CH2OH— CHOH— CHOH— CHOH— CHOH— C— CN  +  H2O  > 

Cyan-hydrine  or  acid  nitrile 

OH 
CH2OH— CHOH— CHOH— CH— CHOH— CHOH— CO  -f  HI 


O 


Lactone  of  hexa-hydroxy  heptanoic  acid 

— >  CH3— CH2— CH2— CH2— CH2— CH2— COOH 

Normal  heptanoic  acid 

In  this  normal  acid  the  carboxyl  group  must  be  joined  to  the  sixth 
carbon  and  this  sixth  carbon  must  be  the  one  which,  in  the  aldose,  was 
in  the  condition  of  carbonyl.  Thus  the  aldehyde  group  in  the  original 
aldo-hexose  must  have  been  the  end  group.  The  constitution  of  the 
aldose  sugars  is,  therefore,  as  has  been  written. 

Position  of  Ketone  Group. — By  exactly  the  same  set  of  reactions  it 
has  been  shown,  from  the  structure  of  the  resulting  acid,  that  in  the 
ketose  sugars  the  ketone  group  is  the  carbon  group  next  to  the  end.  The 
acid  obtained  on  hydrolyzing  the  hydrogen  cyanide  addition  product 
obtained  from  fructose  is  known  as  fructose  carboxylic  acid  and  this 
on  reduction  of  the  hydroxyl  groups  yields  methyl  butyl  acetic  acid, 

CH3— CH2— CH2— CH2— CH— CH3,    or    hexane-2 -carboxylic    acid. 

I 
COOH 

Also  by  an  oxidation  resulting  in  splitting  the  chain  at  the  ketone  group 
fructose  yields  hydroxy  acetic  acid,  CH2OH — COOH  and  tri-hydroxy 
butyric  acid,  HOOC— CH(OH)— CH(OH)— CH2OH. 

We  have  used  hexose  sugars  for  the  purposes  of  illustration  but  the 
reactions  which  we  have  used,  and  the  type  of  formulas  as  proven,  apply 
to  all  simple  carbohydrates  whatever  the  number  of  carbon  atoms. 

Constitution.— Let  us  summarize  the  proofs  for  the  constitution  of 
the  carbohydrates. 

i.  By  the  formation  of  acetyl  derivatives  and  by  the  reduction  to 
normal  hydrocarbons  containing  the  same  number  of  carbon  atoms, 
passing  through  the  poly-hydroxy  alcohols  of  the  same  number  of 
carbons,  carbohydrates  are  poly-hydroxy  alcohols  in  which  each  carbon 
but  one  has  one  and  only  one  hydroxyl  group  linked  to  it. 


324  ORGANIC  CHEMISTRY 

2.  By  the  reaction  with  hydrogen  cyanide,  HCN,  forming  cyan- 
hydrines,   which   are   acid  nitriles,   with  hydroxyl   amine,   H2NOH, 
forming  oximes,  and  with  phenyl  hydrazine,  H2N — NH — C6H5,  forming 
hydrazones,  all  of  which  reactions  are  characteristic  of  the  carbonyl 
group,  carbohydrates  in  water  solution  are  aldehyde  or  kef  one  compounds. 

3.  By  reduction,  with  nascent  hydrogen  (sodium  amalgam),  form- 
ing normal  poly-hydroxy  alcohols,  and  by  the  further  reduction,  by 
means  of  hydrogen  iodide,  HI,  forming  normal  iodo-hydro-carbons, 
carbohydrates  are  compounds  containing  a  normal  or  straight  chain  of 
carbon  groups. 

4.  By  the  three  preceding  reactions  and  by  the  formation  of  carbo- 
hydrates by  the  oxidation  of  poly-hydroxy  alcohols,  carbohydrates  are 
poly-hydroxy  alcohols  in  which  one  alcohol  group  is  oxidized  to  aldehyde 
(primary  alcohol  group  at  the  end  of  the  chain),  or  to  ketone  (secondary 
alcohol  group}. 

5.  By  conversion,  through  the  cyan-hydrine  addition  products  and 
the  hydrolysis  of  these  into  definite  acids  containing  one  more  carbon 
than  the  carbohydrate,  carbohydrates  are  compounds  in  which  the 
aldehyde  group  is  at  the  end  of  the  carbon  chain  and  the  ketone  group  is 
the  second  carbon  group  or  the  one  next  to  the  end. 

That  is,  in  water  solution: 

Carbohydrates  are  aldehyde  or  ketone  oxidation  products  of  normal 
poly-hydroxy  alcohols  of  the  same  number  of  carbon  atoms,  in  which  one 
carbon  group  only  is  oxidized  to  aldehyde  or  ketone,  the  aldehyde  group 
being  the  end  carbon  group  and  the  ketone  group  being  next  to  the  end. 

We  may  then  write  the  constitutional  formulas  for  the  aldo-hexose 
and  the  keto-hexose  as  follows : 

CH2OH— CHOH— CHOH— CHOH— CHOH— CHO 

Aldehyde  carbohydrate,  Aldo-hexose.    Glucose 

CH2OH— CHOH— CHOH— CHOH— CO— CH2OH 

Ketone  carbohydrate,  Keto-hexose.    Fructose 

This  constitution  has  been  shown  to  hold  for  all  simple  carbohy- 
drates and,  until  recently,  has  been  the  accepted  constitution.  In 
referring  to  the  aldehyde  and  ketone  structure  and  the  proofs  for  it  we 
have  repeatedly  stated  that  in  water  solution  the  facts  hold  as  true. 
Recent  study  of  ether  derivatives,  known  as  methyl  glucosides,  formed 
by  reaction  with  methyl  alcohol  have  shown,  however,  that  for  the 


CARBOHYDRATES  325 

actual  substances  another  constitution  is  undoubtedly  the  correct  one. 
This  new  constitution  for  the  carbohydrates  will  be  considered  later 
(p.  345)  in  connection  with  glucose  and  the  other  hexose  carbohydrates. 
The  development  of  our  ideas  in  regard  to  the  relationship  and  classifica- 
tion of  carbohydrates  is,  however,  better  accomplished  by  accepting 
this  earlier  constitution  and,  as  the  reactions  involved  take  place  in 
water  solution,  the  aldehyde  and  ketone  constitution  holds  as  true 
and  will  therefore  be  used  in  the  following  discussion. 

Derivatives  of  Carbohydrates  and  Conversion  of  Carbohydrates 

Oxidation  to  Acids. — By  treatment  with  oxidizing  agents  the  aldose 
carbohydrates  yield  products  resulting  from  the  oxidation  of  the  end 
carbon  groups.  It  is  interesting  that  ordinary  oxidation  affects  only 
these  end  groups.  As  one  of  these  may  be  oxidized  at  a  time  we  obtain, 
first,  mono-basic  acids  and  then  di-basic  acids,  containing  also  unoxi- 
dized  alcohol  groups,  i.e.,  hydroxy  mono-basic  acids  and  hydroxy  di- 
basic acids. 

When  glucose  is  acted  upon  by  chlorine  water,  bromine  water, 
silver  oxide,  or  dilute  nitric  acid,  the  aldehyde  group  is  oxidized  to 
carboxyl  and  a  mono-basic  acid  results. 

CH2OH—  (CHOH)4— CHO  +  O    >     CH2OH— (CHOH)4— COOH 

Glucose  Gluconic  acid 

.Aldo-hexose  Penta -hydroxy  hexan-oic  acid 

By  other  reactions  another  mono-basic  acid  may  be  obtained  in  which 
the  carboxyl  group  is  at  the  other  end  of  the  chain.  This  is  an  alde- 
hyde hydroxy  acid  known  from  its  relation  to  glucose  as  glucuronic  acid 
(p.  253).  It  is  HOOC— (CHOH)4— CHO.  With  strong  oxidizing 
agents,  e.g.,  concentrated  nitric  acid,  the  result  is  a  di-basic  acid, 

CH2OH— (CHOH)4— CHO -f  O    >     HOOC— (CHOH)4— COOH 

Glucose  Saccharic  acid 

Aldo-hexose  Tetra-hydroxy  hexan-di-oic  acid 

Thus,  on  oxidation,  the  aldehyde  sugars  yield  hydroxy  mono-basic 
acids  and  hydroxy  di-basic  acids  of  the  same  number  of  carbon  atoms. 

When,  however,  a  ketone  sugar  is  similarly  oxidized,  the  original 
carbon  chain  is  broken  at  the  ketone  group  and  the  acids  resulting  have 
a  smaller  number  of  carbon  atoms  than  the  carbohydrate. 


326  ORGANIC  CHEMISTRY 

The  keto-hexose,  corresponding  to  the  aldo-hexose  given  above,  is 
oxidized  as  follows : 
CH2OH—  (CHOH)3— CO— CH2OH  +  O        — > 

Fructose 
Keto-hexose 

CH2OH— (CHOH)2— COOH  +  COOH—  CH2OH 

Tri-hydroxy  butyric  Glycolic 

acid  acid 

This  reaction  supports  the  statement  made  a  short  time  ago,  based 
on  other  reactions,  that  the  position  of  the  ketone  group  is  next  to  the 
end  of  the  carbon  chain. 

Phenyl-hydrazine  Reaction. — Hydrazones. — The  reaction  with 
phenyl  hydrazine  has  been  given  as  one  of  the  aldehyde  or  ketone 
reactions  which  prove  the  presence,  in  sugars,  of  the  carbonyl  group. 
The  compounds  resulting  from  this  reaction  are  known  as  hydrazones, 
or  more  specifically  as  phenyl  hydrazones.  With  an  aldo-hexose  the 
reaction  is  as  follows: 

CH(O       +     H2)N— NH— C6H5       -U    CH  =  N— NH— C6H5 

CHOH  CHOH 

(CHOH)3  (CHOH)3 

CH2OH  CH2OH 

Glucose,  Aldo-hexose  Glucose  phenyl  hydrazone 

When,  however,  an  aldose  sugar  is  treated  with  an  excess  of  phenyl 
hydrazine  in  acetic  acid,  the  reaction  does  not  stop  here.  A  second 
molecule  of  phenyl  hydrazine  reacts  as  an  oxidizing  agent,  being  reduced 
itself  to  other  compounds.  As  a  result  of  this  oxidizing  reaction  one 
of  the  secondary  alcohol  groups  of  the  sugar  molecule  residue  of  the 
hydrazone  becomes  oxidized  to  carbonyl.  The  group  oxidized  is  the 
one  next  to  the  original  aldehyde  group  in  the  aldose. 

CH= N— NH— C6H5  CH= N— NH— C2H5 

I  ~H2    ! 

CHOH  (+ C6H5— NH— NH2) >  C  =  O 

(CHOH)3  (CHOH)3 

I  I 

CH2OH  CH2OH 

Glucose  phenyl  hydrazone  Oxidation  product 


CARBOHYDRATE  S  327 

Osazones.  Glucosazone. — This  intermediate  product,  the  oxida- 
tion compound,  containing,  now,  a  new  carbonyl  group,  reacts  with  a 
third  molecule  of  phenyl  hydrazine  forming  a  double  phenyl  hydrazone 
which  is  known  as  an  osazone.  From  glucose  the  osazone  is  known  as 
glucosazone. 
CH  =  N— NH— C6HB  CH  =  N— NH— C6H5 

I  I 

C=(O  +H2)N— NH—  C6H5 >  C  =  N— NH— C6H5 

I  I 

(CHOH)3  (GHOH)3 

CH2OH  CH2OH 

Oxidation  compound  Glucosazone  (an  osazone) 

These  osazones  differ  from  the  first  formed  hydrazones  in  being  less 
soluble  and  more  easily  crystallized.  This  makes  it  possible  to  separate 
sugars  from  each  other  by  converting  them  into  their  osazones. 

Frustosazone. — The  still  more  important  fact  is,  that  the  corre- 
sponding ketose  sugar  which  has  a  different  structure  reacts  in  a  similar 
way  and  yields  exactly  the  same  osazone.  This  means  that  in  the 
ketose  phenyl  hydrazone  the  oxidation  by  means  of  the  second  molecule 
of  phenyl  hydrazine  converts  the  end  carbon  group,  next  to  the  ketone 
group  in  the  original  ketose  into  a  new  aldehyde  group,  giving  a  new 
carbonyl  group  at  the  end  of  the  chain  to  react  with  the  third  molecule 
of  phenyl  hydrazine. 

-H2 

CH2OH  CH2OH+  (C6H5— NH— NH,) > 

I  I 

C  =  (O  +  H2)N— NH— C6H5 >C  =  N— NH— C6H5 

I  I 

(CHOH)3  (CHOH)3 

I  I 

CH2OH  CH2OH 

Keto-hexose,  Fructose  Fructose  phenyl-hydrazone 

CH(O  +  H2)N— NH— C6H5 >CH  =  N— NH— C6H5 

I  I 

C  =  N— NH— C6H5  C  =  N— NH— C6H5 

I  I 

(CHOH)3  (CHOH)3 

I  I 

CH2OH  CH2OH 

Oxidation  compound  Fruct-osazone 

(identical  with  Glucosazone) 


328  ORGANIC  CHEMISTRY 

Osones. — We  are  not  yet  done  with  the  interesting  reactions  of 
these  compounds  for  the  osazones  when  warmed  with  concentrated 
hydrochloric  acid,  take  up  water  and  split  off  the  two  phenyl  hydrazine 
residues  and  yield  a  compound  containing  both  the  aldehyde  and  the 
ketone  groups  of  the  original  aldose  and  ketose  sugars.  The  resulting 
compound  is  known  as  an  osone. 

CH  =  (N— NH— C6H5  +  H2)O  CH  =  O 

C  =  (N— NH— C6H5  +  H2)0  C  =  O 

I  I 

(CHOH)3  (CHOH)3 

CH2OH  CH2OH 

Fructosazone,  Glucosazone  Glucosone,  Osone.     Fructosone 

Finally,  the  osones,  by  reduction  with  nascent  hydrogen,  (Zn  + 
CH3 — COOH),  have  one  of  the  carbonyl  groups  converted  back  into 
the  alcohol  group  and  the  product  is  a  hexose  sugar  such  as  we  started 
with.  The  important  fact,  here,  is,  that  it  is  always  the  end  carbonyl 
which  is  thus  reduced  so  that  the  resulting  sugar  is  always  the  ketose  sugar. 
The  reactions  are, 

CH  =  O  +  H2      >       CH2OH 

I  I 

C  =  O  C  =  O 

(CHOH)3  (CHOH)3 

I  'I 

CH2OH  CHoOH 

Glucosone  Fructose  (keto-hexose) 

Conversion  of  Aldose  into  Ketose. — Therefore,  while  an  aldose 
sugar  and  a  ketose  sugar  yield  the  same  osazone  and  the  same  osone, 
on  the  reduction  of  the  osone  the  ketose  sugar  is  always  obtained.  This 
gives  a  general  method  for  the  conversion  of  an  aldehyde  sugar  into  the 
corresponding  ketone  sugar.  The  phenyl  hydrazine  reaction  is  thus  seen 
to  be  a  very  important  reaction  in  connection  with  carbohydrates  as 
it  enables  us  to  form  well  crystallized  and  separable  osazones  and  also 
to  convert  any  compound  belonging  to  one  of  the  general  classes  of 
carbohydrates,  viz.,  aldoses  into  the  isomeric  compound  of  the  other 
general  class,  viz.,  ketoses. 


CARBOHYDRATES  329 

Increasing  Carbon  Content  of  Aldoses.  —  The  other  two  aldehyde 
reactions  of  sugars,  viz.,  the  reaction  with  hydrogen  cyanide  and  the 
one  with  hydroxyl  amine  are  equally  important  with  the  phenyl  hydra- 
zine  reaction  as,  by  them,  we  are  enabled  to  convert  any  aldose  sugar 
into  another  aldose  sugar  containing,  in  the  one  case,  one  more  carbon 
atom,  and  in  the  other,  one  less  carbon  atom,  than  the  aldose  with  which 
we  started.  That  is  they  are  general  reactions  for  increasing  and  de- 
creasing the  carbon  content  of  aldose  sugars.  The  reactions  apply 
only  to  aldoses.  The  reaction  with  hydrogen  cyanide  by  means  of 
which  we  can  pass  to  the  sugar  containing  one  more  carbon  atom,  takes 
place  in  the  following  steps.  The  hydrogen  cyanide  first  forms  the 
ordinary  aldehyde  addition  compound,  viz.,  the  cyan-hydrine  or  acid 
nitrile.  This  acid  nitrile,  by  hydrolysis  yields  an  acid  which  contains 
one  more  carbon  than  the  original  sugar.  Thus  far  the  reaction  has 
already  been  referred  to  in  connection  with  the  proof  that  the  carbon 
chain  in  carbohydrates  is  a  normal  chain  (p.  322).  Now  by  the  reduc- 
tion of  this  carbon  richer  acid  the  carboxyl  group  is  reduced  to  the 
aldehyde  group  and  the  result  is  an  aldose  sugar  containing  one  more 
carbon  than  the  original  sugar. 

CN  +  2H20       -  > 

! 

CHO  +  HCN      -  >        CHOH 

I  I 

(CHOH)4  (CHOH)4 


CH2OH 

Aldo-hexose  Acid  nitrile 

(Cyan-hydrine) 

COOH  +  H2  -»        CHO 

CHOH  CHOH 

I  I 

(CHOH)4  (CHOH)4 

I  I 

CH2OH  CH2OH 

Hexa-hydroxy  Aldo-heptose 
heptanoic  acid 

Decreasing  Carbon  Content  of  Aldoses.  —  The  reaction  of  hydroxyl 
amine  with  aldose  sugars  is,  in  its  result,  the  reverse  of  the  hydrogen 


330 


ORGANIC  CHEMISTRY 


cyanide  reaction,  i.e.,  it  is  a  general  reaction  for  decreasing  the  carbon 
content  of  aldose  sugars.  The  series  of  reactions  takes  place  in  the  fol- 
lowing manner.  The  hydroxyl  amine  forms,  first,  the  oxime,  as  has 
been  previously  explained,  by  reacting  with  the  aldehyde  group  of  the 
aldose.  The  oximes,  by  loss  of  water,  are  converted  into  cyanogen 
compounds,  i.e.,  acid  nitriles.  When  the  acid  nitriles  are  treated  with 
ammoniacal  silver  solution  the  cyanogen  group  is  split  off  together  with 
a  hydrogen  from  the  neighboring  secondary  alcohol  group.  The  final 
product  is  thus  an  aldose  containing  one  less  carbon  than  the  aldose 
with  which  we  started. 


CH(O  -|-  H2)N— OH 


CHOH 


(CHOH), 


CH2OH 

Aldo-heptose 


H)C  =N— (OH       -H20 


CHOH 


(CHOH), 


CH2OH 

Oxime 

(CN) 


CHO(H      -HCN      CH  =  O 


(CHOH), 


CH2OH 

Acid  nitrile 


(CHOH), 


CH2OH 

Aldo-hexose 


In  practice,  these  reactions  do  not  take  place  quite  as  simply  as 
represented  above.  After  the  formation  of  the  oxime  the  compound  is 
acetylated  and  the  conversion  into  the  acid  nitrile  and  into  the  aldehyde 
occurs  with  these  acetyl  derivatives.  The  resulting  acetyl  derivative 
of  the  aldo-hexose  is  first  converted  into  an  acetamide  compound  which 
on  hydrolysis  yields  the  hydroxyl  compound,  i.e.,  the  aldo-hexose. 

The  decrease  in  the  carbon  content  of  aldose  sugars  may  also  be 
accomplished  by  another  series  of  reactions.  When  the  aldose  is 
oxidized  with  mild  oxidizing  agents,  the  product  is  a  mono-basic  acid, 
containing  the  same  number  of  carbon  atoms.  When  this  hydroxy 
mono-basic  acid  is  treated  with  hydrogen  peroxide,  in  the  presence  of 
ferric  acetate,  a  second  oxidation  takes  place,  by  which  the  secondary 


CARBOHYDRATES 


331 


alcohol  group  next  to  the  carboxyl  is  oxidized  to  carbonyl,  while,  at 
the  same  time,  the  carboxyl  loses  carbon  dioxide.  This  results  in  the 
loss  of  one  carbon  atom  from  the  original  aldose  and  the  formation  of  a 
new  aldehyde  group  from  the  new  end  primary  alcohol. 


CHO 


CHOH 


(CHOH)3 
CH2OH 

Aldo-hexose 


+0 


-CO; 


(COO)H 

CHOH 

(CHOH)  3 


CH2OH 

Mono-basic  acid 
Reactions  of  Carbohydrates 


H 


c=o 


(CHOH); 


CH2OH 

Aldo-pentose 


Fermentation. — Two  general  reactions  of  carbohydrates,  are  of 
importance  not  because  the  products  are  direct  derivatives  of  the  carbo- 
hydrates, but  for  the  commercial  value  of  the  product  itself,  or  for  the 
analytical  use  to  which  the  reaction  may  be  put. 

The  first  general  reaction  includes  several  that  are  embraced  in  the 
term  fermentations.  Certain  of  the  carbohydrates,  when  acted  upon 
by  definite  micro-organisms  (molds,  fungi  or  bacteria) ,  undergo  decom- 
position and  the  result  is  definite  in  each  case.  We  have  referred  to 
the  formation  of  lactic  acid  by  the  action  of  certain  bacteria  upon  milk 
sugar  or  upon  cane  sugar.  We  have,  also,  in  connection  with  the  sub- 
ject of  alcoholic  fermentation,  in  which  glucose  is  decomposed  by  the 
enzyme,  zymase,  which  is  secreted  by  the  yeast  plant,  discussed  sugar 
fermentation  in  so  far  as  this  particular  process  and  the  products  of  it 
are  concerned.  This  fermentation  is  represented  by  the  reaction, 


C6Hi206  +  zymase 

Glucose 


2C2H5OH 

Ethyl  alcohol 


2CO2 


So  far  as  the  sugars  themselves  are  concerned,  it  is  interesting,  that, 
they  possess  very  distinct  and  definite  characters  in  their  relation  to  the 
yeast  enzyme,  zymase.  Of  the  simple  sugars  it  is  only  those  containing 
three,  six  or  nine  carbon  atoms,  i.e.,  C3H6O3,  C6Hi2O6,  CgHisOg,  which 
are  able  to  be  fermented  by  this  particular  enzyme.  Furthermore  the 
different  six  carbon  sugars,  or  hexoses,  which  we  shall  presently  con- 
sider in  detail,  possess  considerable  difference  as  to  the  ease  of  fermen- 


332  ORGANIC  CHEMISTRY 

tation.  It  has  also  been  shown,  by  Emil  Fischer,  that  the  relation  of 
sugars  to  enzyme  action  is  closely  connected  with  the  stereo-chemical 
configuration  of  the  sugar  molecule.  The  bacterial  fermentation  of 
sugars  is  of  an  entirely  different  type  from  that  of  the  alcoholic  fermen- 
tation due  to  zymase.  The  products  of  this  latter  class  of  fermentations 
are  chiefly  acids,  especially  lactic,  butyric,  acetic  and  carbonic.  In 
some  cases  alcohol  may  be  formed  and  also  poly-hydroxy  alcohols  and 
gum-like  substances.  Special  fermentations  of  importance  will  be 
considered  under  each  sugar  as  it  is  described  later. 

Reduction  of  Fehling's  Solution. — The  reaction  of  sugars  with  an 
alkaline  tartrate  solution  of  copper  sulphate,  known  as,  Fehling's  solu- 
tion, while  not  giving  any  information  as  to  the  constitution  of  sugars, 
is  of  importance  in  distinguishing  certain  sugars  and  other  carbohy- 
drates, and  of  still  more  value  as  the  basis  of  analytical  methods  for 
their  quantitative  determination. 

Fehling's  solution  is  an  empirical  solution,  usually  made  as  follows: 

Solution  A.  Copper  sulphate,  CuSO4  5H2O 69.30  gm.  per  liter. 

Solution  B.  Potassium  hydroxide,  KOH 250      gm.  per  liter. 

Sodium-potassium  tartrate,        — 346      gm.  per  liter. 

Rochelle  salt. 

The  following  compound  is  believed  to  be  present. 

Na(OOC-HCOx 

I     >Cu) 
K(OOC-HC(/ 

In  this  salt  the  copper  is  not  the  cation  but  is  part  of  the  anion 
and,  therefore,  is  not  precipitated  by  the  alkali  as  copper  hydroxide. 

The  two  solutions,  A  and  B,  are  kept  separate  and  when  used  are 
mixed  in  equal  volumes.  Several  modifications  of  the  solution  have 
been  suggested.  Benedict  uses  200  gm.  of  anhydrous  sodium  car- 
bonate instead  of  potassium  hydroxide,  and  also,  substitutes  for  the 
Rochelle  salt  the  following  mixture : 

Potassium  citrate  — 400  gm. 

Potassium  thio-cyanate -250  gm. 

Potassium  ferro-cyanide — • — 0.5  gm. 


CARBOHYDRATES  333 

These  modifications  give  a  solution  especially  designed  for  the 
determination  of  small  amounts  of  sugar  as  it  is  found  in  human  urine. 
The  modified  solution  also  has  the  advantage  that  it  can  be  kept  in 
the  mixed  condition.  The  reaction  of  sugars  with  Fehling's  solution 
consists  in  the  reduction,  by  the  sugar,  of  the  cupric  copper  of  the 
solution  with  the  precipitation  of  red  insoluble  cuprous  oxide,  Cu2O. 
The  method,  as  applied  in  analysis,  is  wholly  empirical,  and  rests  upon 
the  previous  accurate  determination  of  the  exact  amount  of  cuprous 
oxide  precipitated  by  definite  amounts  of  pure  sugars  when  solutions 
of  them,  of  approximate  concentrations,  are  boiled  for  a  definite  time 
under  definite  conditions.  These  definite  determinations  have  been 
made  for  each  one  of  several  sugars  and  the  results  have  been  tabulated 
and  are  used  in  all  subsequent  determinations. 

Jn  addition  to  its  quantitative  application  Fehling's  solution  serves 
as  a  qualitative  test  for  certain  sugars.  As  will  be  given  under  each  of 
the  different  sugars  certain  ones  have  the  property  of  reducing  Fehling's 
solution  while  others  do  not.  When  used  as  a  qualitative  test  a  small 
amount  of  Fehling's  solution  is  mixed  with  a  small  amount  of  the  sup- 
posed sugar  solution  and  then  boiled.  The  appearance  of  a  red  pre- 
cipitate of  cuprous  oxide  proves  the  presence  of  some  sugar  possessing 
the  property  of  reducing  Fehling's  solution.  The  property  of  reducing 
Fehling's  solution,  in  the  case  of  sugars,  probably  rests  in  the  presence 
of  the  aldehyde  or  ketone  group  in  the  molecule.  The  products  of  this 
reaction,  so  far  as  the  sugar  itself  is  concerned,  are  probably  unknown. 

Chemical  Classification  of  Carbohydrates 

We  have  already  developed  several  facts  in  regard  to  the  chemical 
classification  and  nomenclature  of  those  carbohydrates  which  are 
sugars.  These  facts  may  be  summarized  as  follows: 

1.  The  termination  ose,  is  given  to  all  carbohydrate  classes  and  to 
those  individuals  which  have  sugar  character,  e.g.,  mono  saccharoses, 
glycerose,  glucose,  etc. 

2.  The  numerical  prefixes,  bi-,  tri-,  tetra-,  etc.,  are  used  to  indicate 
the  number  of  carbon  atoms  in  the  molecule,  e.g.,  CaH-tOs-Tri-ose, 


3.  Each  of  the  different  groups  of  simple  sugars,  from  tri-oses  to 
non-oses,  exists  in  two  structurally  isomeric  forms:  (a)  that  of  a  poly- 
hydroxy  aldehyde,  and  (b)  that  of  a  poly-hydroxy  ketone.  To  cUs- 


334  ORGANIC  CHEMISTRY 

tinguish  between  these  two  forms  we  use,  for  the  former,  the  name 
aldose,  and  for  the  latter,  the  name  ketose.     Thus  we  may  have, 

an  aldo-pentose  and  a  keto-pentose, 
an  aldo-hexose  and  a.  keto-hexose,  etc. 

Mono-saccharoses. — The  carbohydrates,  or  saccharoses,  then,  are 
divided  into  two  large  classes,  viz.,  mono-saccharoses  and  poly-sac- 
charoses. 

I.  Mono-saccharoses  are  simple  sugars  which  are  not  able  to  be  split 
by  hydrolysis  into  any  simpler  sugars,  hence  the  name  which  signifies 
unit  sugars.  They  have  the  general  formula,  CnH2nOn,  and  they  range 
in  composition  from  bi-oses,  containing  two  carbon  atoms,  to  non-oses 
containing  nine  carbon  atoms.  Each  one  also  with  the  exception  of 
the  bi-oses  is  known  both  as  an  aldose  and  a  ketose. 
Biases  C2H4O2 

Trioses  C3H6O3  (Aldose  +  Ketose) 
Tetroses  C^sCh  Aldose  and  Ketose 
Pentoses  CsHioOs  Aldose  and  Ketose 
Hexoses  CeH^Oe  Aldose  and  Ketose 
Heptoses  CyHuO?  Aldose  and  Ketose 
Octoses  CgHieOg  Aldose  and  Ketose 
Nonoses  CgHigOg  Aldose  and  Ketose 

Poly-saccharoses. — (II)  Poly-saccharoses,  as  the  name  indicates, 
are  not  simple  sugars,  but  are  multiples  of  the  unit  sugars.  On  hydro- 
lysis, they  split  into  two  or  more  molecules  of  one  of  the  simple  sugars, 
or  mono-saccharoses.  This  class  is  further  sub-divided  into  two  sub- 
classes due  to  the  fact  that  some  of  them  are  compounds  possessing 
true  sugar  characters,  while  others  are  not  true  sugars. 

(IIa)  Poly-saccharoses  that  are  true  sugars.  The  members  of  this 
sub-class  consist  of  two  groups,  only  one  of  which  is  of  great  importance. 
Di-saccharoses  or  Hexo-bioses. — (i)  The  first  group  is  known  as 
di-saccharoses.  These  are  so  called  because  they  split,  on  hydrolysis, 
into  two  molecules  of  hexose  mono-saccharoses.  The  general  formula 
for  these  di-saccharoses  is  CnH2n_2On_i,  and  the  known  members  all 
have  the  composition  formula  Ci2H22On.  They  are  represented  by 
such  common  substances  as  cane  sugar,  milk  sugar  and  malt  sugar. 
The  reaction  of  hydrolysis  is, 

Ci2H22Ou  +  H2O     »     2C6H12O6 


CARBOHYDRATES  335 

On  this  account  they  are  also  called  hexo-bioses,  which  term  is  some- 
what confusing  because  of  the  different  meaning  given  to  the  word 
bi-oses. 

Tri-saccharoses  or  Hexo-trioses.  —  (2)  The  other  less  important 
group  of  the  poly-saccharoses  that  are  true  sugars  is  that  of  the  tri- 
saccharoses,  or  hexo-trioses.  These  split,  as  their  name  indicates, 
into  three  molecules  of  hexose  mono-saccharoses.  The  formula  cor- 
responds to  the  composition  CisH^Oie.  The  hydrolysis  may  be 
represented  by  the  reaction, 

C18H32016  +  2H20         -*      3CeH1206 

Poly-saccharoses  not  True  Sugars.  —  (lib)  The  second-sub-class  of 
poly-saccharoses  consists  of  those  carbohydrates  which  are  not  true 
sugars.  This  group  is  represented  by  such  substances  as  starch, 
dextrin  and  cellulose.  The  group  is  usually  known  by  the  simple 
name,  poly-saccharoses,  as  the  specific  names,  di-saccharoses  and  tri- 
saccharoses,  are  used  for  the  members  of  the  first  subclass.  We  do  not 
know  how  many  molecules  of  mono-saccharoses  are  obtained  from  one 
molecule  of  these  poly-saccharoses,  because  we  do  not  know  the  mole- 
cular weight  of  the  compounds.  They  are  represented  by  the  empirical 
formula  (CsHioOs)*,  and  their  hydrolysis  may  be  represented  as  follows: 

(CeHioOs)*  4-  xH2O       ~r»    xC6H12O6 

Summarizing  our  classification  of  the  carbohydrates  we  have, 
(i)  Mono-saccharoses,  aldoses  and  ketoses. 

C2H4O2,  Bioses  to  C9H18O9,  Nonoses 
These  do  not  hydrolyze  to  any  simpler  sugars. 
(II)  Poly-saccharoses. 

(a)  True  Sugars. 

(i)  Di-saccharoses,  or  Hexo-bioses, 


These  hydrolyze  to  two  molecules 
of  mono-saccharoses,  C6Hi2O6. 
(2)  Tri-saccharoses,  or  Hexo-trioses, 

CigHssOie 

These  hydrolyze  to  3C6Hi2O6. 
(b)  Not  true  sugars. 

Poly-saccharoses,    (C6Hi0O5)x. 
These  hydrolyze  to  xC6Hi2O6. 


336  ORGANIC  CHEMISTRY 

Having  thus  established  our  system  of  classification  of  the  car- 
bohydrates as  based  upon  their  constitution,  we  are  now  ready  to  take 
up  the  various  individual  members  and  study  them  as  to  their  occur- 
rence, general  properties,  and  commercial  uses.  Also  as  to  their 
specific  relation  to  eac  i  other  and  special  oints  in  regard  to  their 
constitution. 

A.  MONO-SACCHAROSES.     CnH2nOn 
I.  BIOSES.     C2H402 

Plainly,  the  simplest  compound  which  contains  both  alcohol  and 
aldehyde  groups  is  the  compound  derived  from  ethane  by  the  oxidation 
of  one  of  the  methyl  groups  to  alcohol  and  the  other  to  aldehyde,  or 
from  ethylene  glycol  by  the  oxidation  of  one  of  the  alcohol  groups  to 
aldehyde,  viz., 

CH3  CH2OH  CHO 

CH3  CH2OH  CH2OH 

Ethane  Ethylene  glycol  Glycolic  aldehyde 

This  compound  has  already  been  mentioned  and  is  known  as  gly- 
colic  aldehyde.  According  to  our  system  of  classification  and  of  naming 
the  carbohydrates  this  compound  would  be  a  biose,  or  a  two  carbon 
sugar.  Glycolic  aldehyde  does  not,  however,  possess  the  general 
characters  of  a  sugar  and  though  it  is  truly  the  simplest  representative 
of  the  carbohydrates  it  is  not  usually  included  as  such. 

II.  TRIOSES.     C3H603 

The  alcohol-aldehyde  compound  containing  three  carbon  atoms, 
i.e.,  a  triose,  has  also  been  referred  to  (p.  229).  It  is  the  compound 
usually  regarded  as  the  simplest  sugar.  While  the  biose,  just  ref  rred 
to,  cannot  exist  as  a  ketone-alcohol  compound,  the  triose  can  exist  both 
as  the  aldehyde  alcohol  and  also  as  the  ketone  alcohol  compound.  It  is 
obtained,  as  has  been  previously  stated,  by  the  oxidation  of  the  three 
carbon  tri-hydroxy  alcohol,  glycerol.  On  this  account  it  has  been  given 
the  name  of  glycerose.  The  substance  known  as  glycerose  is  not  an 
individual  compound  of  the  aldehyde  or  ketone  constitution,  but  is  a 
mixture  of  both  of  these  compounds,  as  they  are  formed  by  the  oxidation 
of  glycerol. 


MONO-SACCHAROSES  337 

CH2OH                       CHO  CHoOH 

I                   +0          |  | 

CHOH                         CHOH  and          C  =  O 

CH2OH                       CH2OH  CH2OH 

Glycerol                             Glyceric  aldehyde  Di-hydroxy  acetone 

an  Aldose  a  Ketose 


Glycerose 

The  oxidation  of  glycerol  may  be  accomplished  by  means  of  several 
reagents,  e.g.,  dilute  nitric  acid,  bromine,  bromine  and  sodium  car- 
bonate, platinum  black,  etc.  The  best  method,  in  practice,  is  to 
oxidize  the  lead  salt  of  glycerol  by  means  of  bromine  vapor.  By  such 
oxidation  it  is  mostly  the  ketone  compound  which  is  formed,  though 
the  aldehyde  is  always  present.  As  obtained,  glycerose  is  a  sweet 
syrup  which  readily  reduces  Fehling's  solution,  reacts  with  phenyl 
hydrazine,  forming  osazones,  and  is  fermentable  by  yeast  zymase 
yielding  alcohol.  The  most  important  fact  in  connection  with  gly- 
cerose is  that  it  polymerizes  easily,  under  the  influence  of  alkalies,  and 
yields  a  keto-hexose.  This  polymerization  takes  place  by  a  condensation 
exactly  analogous  to  the  aldol  condensation. 
CH2OH— CHOH— CHO  +  HCH  OH— CO— CH2OH  > 

Aldo-triose  Keto-triose 

CH2OH— CHOH— CHOH— CHOH— CO— CH2OH 

Keto-hexose 

We  shall  consider  this  condensation  again  when  we  consider  the 
hexose  sugars. 

III.  TETROSES.     C4H8O4 

A  tetrose,  known  as  erythrose,  has  been  obtained  by  the  oxidation 
of  the  tetra-hydroxy  alcohol,  erythritol,  or  butan-tetrol. 
CH2OH— CHOH— CHOH— CH2OH  +  O  — » 

Erythrito1  CH2OH— CHOH— CHOH— CHO 

Erythrose 

It  has  also  been  prepared  by  the  aldol  condensation  of  glycolic 
aldehyde, 
CH2OH— CHO  +  HCH  OH— CHO  -» 

Glycolic  aldehyde  CH2OH— CHOH— CHOH— CHO 

Erythrose 

Erythrose  yields  an  osazone  with  phenyl  hydrazine  and  reduces 
Fehling's  solution  but  is  not  fermentable  with  yeast  zymase.     When 
22 


ORGANIC  CHEMISTRY 

oxidized,  by  strong  oxidizing  agents,  to  a  di-basic  acid  it  yields  tartaric 

acid. 

CH2OH—  CHOH—  CHOH— CHO   +   O   > 

Erythrose 

HOOC— CHOH— CHOH— COOH 

Tartaric  acid 

IV.  PENTOSES.     CfiHioOs 

Pentose  sugars  may  be  obtained  by  the  oxidation  of  the  normal  penta- 
hydroxy  alcohol.    The  usual  method  of  preparing  them,  however,  is 
by  decreasing  the  carbon  content  of  a  hexose  sugar  by  means  of  the  oxime 
reaction  (p.  330). 
CH2OH—(CHOH)3— CHOH— CHO        > 

Aldo-hexose  Oxime  reaction 

CH2OH—  (CHOH)  3— CHO 

Aldo-pentose 

Pentosans. — The  importance  of  the  pentose  sugars  lies  in  their  wide 
distribution,  in  nature,  in  the  pectins  and  gummy  substances  of  many 
plants.  The  chief  sources  of  two  of  the  pentose  sugars  are  gum  Arabic 
and  wood  gum.  In  the  pectins  and  other  substances  of  plants  the  pen- 
toses  do  not,  probably,  occu-  free,  but  in  the  form  of  complex  sub- 
stances known  as  pentosans.  When  these  pentosans  are  boiled  with 
acid,  hydrolysis  takes  place  and  the  pentose  is  set  free.  The  pento- 
sans therefore  bear  the  same  relation  to  pentoses  that  the  polysac- 
charoses  do  to  the  hexoses,  i.e.,  they  are  polypentoses.  When  a  pentose 
sugar  is  heated  with  strong  hydrochloric  acid  and  distilled,  it  is  de- 
composed and  yields  furfural  which  distils  over.  Furfural  is  a  cyclic 
compound,  to  be  considered  later  (Pt.  II),  to  which  the  following  for- 
mula has  been  given, 

CH— CH 

II        II 
HC        C— CHO        Furfural 

\/ 
O 

When  an  acid  solution  of  phloroglucinol  (Pt.  II)  is  added  to  furfural 
a  black  precipitate,  known  as  a  phloroglucid,  is  formed.  From  the 
weight  of  this  phloroglucid  we  may  calculate,  by  empirical  methods,  the 
amount  of  furfural  and,  from  this,  the  amount  of  pentose  sugar  with 
which  we  started,  or  also,  the  amount  of  pentosan.  This  is  the  basis 
of  the  analytical  method  for  the  determination  of  pentosan  compounds 
in  plant  materials.  As  the  pentosans  possess  considerable  nutritive 


MONO-SACCHAROSES  339 

value  as  foods,  especially  in  stock  feeds,  their  determination  is  of  im- 
portance. 

Ariabnose,  CH2OH— (CHOH)s— CHO 

This  sugar  is  an  aldo-pentose,  and  is  obtained,  synthetically,  by 
degrading  a  certain  stereo-isomeric  hexose  sugar  known  as  mannose. 
It  may  also  be  obtained,  as  the  name  indicates,  and  as  has  been  stated 
above,  by  hydrolyzing  gum  Arabic  or  cherry  gum.  It  is  crystalline 
and  melts  at  about  160°.  It  has  a  sweet  taste  and  is  optically  active, 
being  dextro  rotatory.  It  forms  an  osazone  which  melts  at  157°- 
158°.  By  reduction  it  yields  arabitol,  a  penta-hydroxy  alcohol.  On 
oxidation  with  strong  oxidizing  agents  it  yields  a  di-basic  acid,  viz., 
tri-hydroxy  glutaric  acid, 
CH2OH— CHOH— CHOH— CHOH— CHO  +  O  > 

Arabinose 

COOH— CHOH— CHOH— CHOH— COOH 

Tri-hydroxy  glutaric  acid 
Xylose,  CH2OH—  (CHOH)  3—  CHO 

This  sugar  is  also  an  aldo-pentose  and  is  stereo-isomeric  with  arabi- 
nose.  It  is  known  as  wood  sugar  because  it  is  obtained  by  the  hydroly- 
sis of  wood  gum,  i.e.,  of  the  pentosans  present  in  this  gum.  It  is 
crystalline  and  melts  at  140°-!  60°.  It  is  optically  active,  being  dextro- 
rotatory. Its  osazone  melts  at  160°.  By  reduction  it  yields  a  penta- 
hydroxy  alcohol  and  by  oxidation  it  yields  tri-hydroxy  glutaric  acid. 
Khamnose,  C6H12O5,  CHs— CHOH— (CHOH)  r-CHO 

As  will  be  seen  from  the  above  formula,  rhamnose  is  an  example  of 
a  carbohydrate  in  which  the  hydrogen  and  oxygen  are  not  in  the 
proportion  of  H2O.  It  has  been  proven  to  have  the  constitution  of  a 
methyl  substitution  product  of  a  pentose  sugar.  It  is  obtained  by  the 
hydrolysis  of  certain  glucosides.  It  is  crystalline  and  the  crystals 
contain  one  molecule  of  water.  The  anhydrous  sugar  melts  at  93°. 
It  tastes  sweet,  is  dextro  rotatory  and  its  osazone  melts  at  180°. 

V.  HEXOSES.     C6H1206 

Synthesis  from  Poly-alcohols. — We  come,  now,  to  that  group  of 
mono-saccharoses,  the  hexose  mono-saccharoses,  which  contains  the 
most  important  simple  sugars  which  are  known,  viz.,  glucose  and  fruc- 
tose. The  hexoses  may  be  prepared,  synthetically,  by  oxidizing  the 
hexa-hydroxy  alcohols,  e.g.,  mannitol,  dulcitol,  sorbitol,  etc.  (p.  219). 

Naturally  occurring  substances  are  known  in  the  two  structural 
forms  of  aldo-hexoses  and  keto-hexoses. 


340  ORGANIC  CHEMISTRY 

Glucose,  CH2OH—  CHOH—  CHOH—  CHOH—  CHOH—  CHO, 

Aldo-hexose. 

Fructose,  CH2OH—  CHOH—  CHOH—  CHOH—  CO—  CH2OH, 

Keto-hexose. 

The  aldo-hexose  is  the  commonly  known  and  widely  distributed 
substance  glucose  or  grape  sugar,  The  keto-hexose  is  also  widely 
distributed  but  less  commonly  known.  It  is  called  fructose  or  fruit 
sugar.  The  constitution  of  these  two  sugars,  glucose  as  an  aldo- 
hexose  and  fructose  as  a  keto-hexose  has  been  proven  by  the  reactions 
already  discussed  as  proving  the  position  of  the  aldehyde  and  the  ketone 
group  (p.  322). 

From  Glycerose.  —  A  second  synthesis  of  hexoses  is  the  aldol  con- 
densation of  glycerose,  as  already  referred  to  (p.  337).  As  glycerose 
is  a  mixture  of  the  two  compounds,  glyceric  aldehyde  (aldo-triose), 
and  di-hydroxy  acetone  (keto-triose)  ,  the  condensation  product  is  the 
keto-hexose,  or  fructose. 
CH2OH—  CHOH—  CHO  +  HCH  OH—  CO—  CH2OH  -  > 


CH2OH—  CHOH—  CHOH—  CHOH—  CO—  CH2OH 

Fructose 

Keto-hexose 

If,  instead  of  condensing  glycerose,  we  condense  the  aldo-triose,  glyceric 
aldehyde,  by  itself,  we  then  obtain  the  aldo-hexose,  or  glucose. 
CH2OH—  CHOH—  CHO  +  HCHOH—  CHOH—  CHO        --  > 

Glyceric  aldehyde 

Aldo-triose 

CH2OH—  CHOH—  CHOH—  CHOH—  CHOH—  CHO 

Glucose 

Aldo-hexose 

From  Formaldehyde.-  —  Historically  and  physiologically,  the  most 
important  synthesis  of  hexose  mono-saccharoses  is  from  formaldehyde. 
In  1  86  1  Butlerow  found  that  dioxymethylene  (tri-oxymethylene)  ,  pro- 
duced by  polymerizing  formaldehyde,  yielded  with  hot  lime  water  a 
sweet  substance  to  which  he  gave  the  name  of  methylenitan.  The 
substance  reduced  Fehling's  solution,  but  was  optically  inactive  and 
non-fermentable  with  yeast  zymase.  Later,  Loew  obtained  a  sweet, 
non-fermentable  syrup  by  the  direct  action  of  lime-water  on  formalde- 
hyde. This  substance  he  called  formose.  He  afterward  obtained 
what  he  considered  another  sugar  by  the  action  of  magnesium  hydroxide 
upon  formaldehyde.  This  substance  was  fermentable  by  yeast  and 
to  it  he  gave  the  name  of  methose.  In  1887,  Fischer  and  Tafel 


MONO-SACCHAROSES 


341 


obtained,  by  the  action  of  barium  hydroxide  upon  acrolein  di-bromide, 
and  also  by  the  condensation  of  glycerose,  by  means  of  alkalies  (p. 
337),  a  sugar  which  they  called,  a-acrose,  and  which  they  showed  was 
identical  with  inactive  fructose.  They  also  showed  that  the  three 
substances  just  mentioned,  prepared  by  Butlerow  and  Loew  were, 
probably  identical  with  this  new  one.  This  was  the  first  time  that  a 
hexose  mono-saccharose  had  ever  been  synthesized  and  the  impor- 
tance of.  this  work  can  hardly  be  realized.  As  we  shall  discuss  later, 
the  synthesis  of  hexose  sugars  from  formaldehyde  is  of  fundamental 
importance  in  connection  with  the  process  of  photo-synthesis  in  the 
leaves  of  green  plants.  We  may  summarize  the  synthetic  reactions 
above  mentioned  in  the  following  way. 

H  CH(OH) 

— >         Polymerization         >  /\ 

H— C  =  O       I  (HO)HC  —  CH(OH) 

Formic  aldehyde  Tri-oxymethylene 


Ca(OH)2 

or 
Mg(OH)2 


+  Ca(OH)2 


CH2OH— CHOH— CHOH— CHOH— CO  — CH2— OH 

a-Acrose,  or  inactive  Fructose  (Methose 


Ba(OH) 


by  Aldol 
condensation 


CH2Br— CHBr— CHO 

Acrolein  di-bromide 


CH2OH—  CHOH—  CHO 


CH2OH—  CO—  CH2OH 


Glycerose 


342  ORGANIC  CHEMISTRY 

Hydrolysis  of  Poly-saccharoses. — The  most  important  relationship 
of  the  hexose  sugars  is  that  involved  in  the  common  method  for  their 
preparation.  Poly-saccharoses,  e.g.,  cane  sugar  and  starch,  hydrolyze 
and  split  into  two  or  more  molecules  of  hexose  sugars.  On  the  hydrolysis 
of  a  di-saccharose  two  molecules  of  hexose  sugars  result.  These  two 
molecules  may  be  the  same  hexose  sugar  or  they  may  be  different. 
When  a  true  poly-saccharose,  like  starch,  is  hydrolyzed  more  than  two 
molecules  of  hexose  sugar  result.  These  hydrolytic  reactions  will  be 
considered  in  detail  under  the  different  poly-saccharoses. 

Stereo-isomerism  of  the  Mono -saccharoses 

It  will  be  necessary,  now,  to  consider  the  stereo-isomerism  of  those 
mono-saccharoses  which  contain  more  than  three  carbon  atoms.  The 
isomerism  of  the  aldoses  and  ketoses  is  structural,  depending  upon  the 
different  groups  present  in  the  molecule.  These  two  isomeric  forms 
of  the  mono-saccharoses  are  found  in  the  case  of  each  member  above 
the  bi-ose  group,  as  this  can  exist  only  in  the  condition  of  an  aldehyde 
compound  and  not  as  a  ketone.  If  we  examine  the  structural  formula 
of  any  mono-saccharose  containing  more  than  three  carbons  we  shall 
find  that  they  each  contain  at  least  one  asymmetric  carbon  atom.  In 
most  cases  two  or  more  asymmetric  carbons  are  present,  as  shown  in  the 
following  formulas  in  which  the  asymmetric  carbon  atoms  are  marked. 

CH2OH— CHOH— CHOH— CHO,  A  Ido-tetrose. 

CH2OH— CHOH— CO— CH2OH,  Keto-tetrose. 

CH2OH— CHOH— CHOH— CHOH— CHOH— CHO,    A  Ido-hexose. 

CHoOH— CHOH— CHOH— CHOH— CO— CH2OH,  Keto-hexose. 
In  the  case  of  glyceric  aldehyde  we  also  have  an  asymmetric  carbon  and 
should  have  stereo-isomerism,  but  in  the  case  of  this  compound  such 
isomers  are  unknown.  In  the  following  discussion  we  shall  use  only 
the  hexose  sugars  and  the  aldose  form  of  these.  A  fuller  discussion  of 
the  stereo-isomerism  of  these  compounds,  involving  all  compounds, 
will  be  found  in  larger  books,  such  as  Cohen,  and  Meyer  and  Jacobson. 
Number  of  Stereo-isomers. — Plainly,  with  more  than  one  asym- 
metric carbon  atom  in  the  molecule,  we  can  have  more  than  two  stereo- 
isomers,  as  we  had  in  the  case  of  lactic  acid.  When  we  speak  of  the 
number  of  stereo-isomers  we  do  not  include  the  racemic  form1  as  it 


MONO-SACCHAROSES  343 

is  made  up  of  the  two  optical  isomers.  Thus  in  lactic  acid  we  say  there 
are  two  stereo-isomers  and  in  tartaric  acid  there  are  three.  In  the 
latter  case  we  include  the  meso-tartaric  acid  as  it  is  an  unresolvable 
inactive  form.  Nor  do  we  mean  that  the  stereo-isomers  all  possess 
different  optical  activity,  as  here,  of  course  we  can  have  only  two  forms, 
viz.,  the  dextro  and  the  lew.  We  mean  by  stereo-isomers  any  two,  or 
more  compounds,  in  which,  considering  all  the  asymmetric  carbon 
atoms  present,  there  is  a  different  space  configuration.  Two  such 
isomers  may,  or  may  not,  have  the  same  optical  activity,  or  they  may 
be  optically  inactive,  by  intra-molecular  compensation. 

From  a  study  of  stereo-isomerism,  van't  Hoff  has  developed  the 
following  formula  as  expressing  the  number  of  stereo-isomers  possible 
with  any  number  of  asymmetric  carbon  atoms,  when  the  compound 
is  unsymmetrical  in  that  the  two  halves  are  unlike.  If  n  represents 
the  number  of  asymmetric  carbon  atoms  in  the  molecule,  then,  A  = 
2n,  in  which  A  is  the  number  of  stereo-isomers  which  may  be  formed. 
In  a  compound,  like  an  aldo-hexose,  just  given,  in  which  there  are  four 
asymmetric  carbon  atoms,  we  have  according  to  the  above  formula, 
n  =  4  therefore  A  =  24  =  16.  This  formula  applies  only  in  the  case  of 
compounds  in  which  the  two  halves  of  the  compound  are  unlike,  as 
with  the  aldo-hexoses,  but  not  in  the  case  of  compounds,  like  tartaric 
acid,  in  which  the  two  halves  of  the  compound  are  alike.  The  mono- 
basic acids  resulting  from  the  aldo-hexoses  are  also  unsymmetrical 
and  hold  to  the  van't  Hoff  formula.  The  dibasic  acids  and  the  poly- 
hydroxy  alcohols,  resulting  from  the  aldo-hexoses  are,  however,  un- 
symmetrical only  in  case  they  contain  an  odd  number  of  carbon  atoms, 
i.e.,  pentose,  heptose  and  nonose  derivatives.  With  the  like  deriva- 
tives of  mono-saccharoses  containing  an  even  number  of  carbons,  i.e., 
tetroses,  hexoses,  and  octoses,  we  have  as  in  tartaric  acid,  a  symmetrical 
compound  in  which  the  two  halves  of  the  molecule  are  alike  and  in 
such  compounds  the  formula  of  van't  Hoff  does  not  hold.  In  all 
compounds  of  this  latter  type  we  have  the  formation  of  inactive  com- 
pounds of  the  character  of  meso-tartaric  acid.  On  the  next  page  we 
give  the  space  configuration  of  all  the  sixteen  possible  stereo-isomers 
of  the  aldo-hexose  sugar,  viz.,  CH2OH— CHOH— CHOH— CHOH— 
CHOH — CHO,  C6Hi2O6,  the  commonly  occurring  form  of  which  is  the 
well  known  glucose  or  grape-sugar.  The  dibasic  acid  obtained  from 
each  isomer  is  also  indicated.  It  is  a  striking  confirmation  of  the 


344 


ORGANIC  CHEMISTRY 


theories  of  stereo-chemistry  that,  of 
aldo-hexoses,  fourteen  are  known  at 


the  possible  sixteen  stereo-isomeric 
the  present  time. 


CHO 

CHO 

CHO 

CHO 

! 

1 

I 

1 

HO—  C—  H 

H—  C—  OH 

H—  C—  OH 

HO—  C—  H 

1 

1 

1 

1 

HO—  C—  H 

H—  C—  OH 

HO—  C—  H 

H—  C—  OH 

1 

1 

1 

1 

H—  C—  OH 

HO—  C—  H 

H—  C—  OH 

HO—  C—  H 

1 

1 

1 

1 

H—  C—  OH 

HO—  C—  H 

HO—  C—  H 

H—  C—  OH 

1 

1 

1 

1 

CH2OH 

CH2OH 

CH2OH 

CH2OH 

d-Mannose 

1-Mannose 

d-Idose 

l-Idose 

to 

to 

to 

to 

d-Manno-saccharic 

1-Manno  -saccharic 

d-Ido-saccharic 

1-Ido-saccharic 

acid 

acid 

acid 

acid 

CHO 

CHO 

CHO 

CHO 

j 

1 

1 

1 

H—  C—  OH 

HO—  C—  H 

HO—  C—  H 

H—  C—  OH 

1 

1 

1 

1 

HO—  C—  H 

HO—  C—  H 

H—  C—  OH 

H—  C—  OH 

1 

1 

1 

! 

H—  C—  OH 

H—  C—  OH 

HO—  C—  H 

HO—  C—  H 

1 

1 

1 

1 

H—  C—  OH 

HO—  C—  H 

HO—  C—  H 

H—  C—  OH 

1 

I 

1 

1 

CH2OH 

CH2OH 

CH2OH 

CH2OH 

d-Glucose 

d-Gulose 

l-Glucose 

l-Gulose 

to 

to 

d  -Saccharic 

acid 

1  Saccharic  acid 

CHO 

CHO 

CHO 

CHO 

1 

1 

-1 

I 

H—  C—  OH 

HO—  C—  H 

H—  C—  OH 

HO—  C—  H 

1 

1 

1 

1 

HO—  C—  H 

H—  C—  OH 

H—  C—  OH 

HO—  C—  H 

1 

1 

1 

1 

HO—  C—  H 

H—  C—  OH 

H—  C—  OH 

HO—  C—  H 

1 

1 

1 

1 

H—  C—  OH 

HO—  C—  H 

H—  C—  OH 

HO—  C—  H 

I 

1 

1 

1 

CH2OH 

CH2OH 

CH2OH 

CH2OH 

d-Galatose 

l-Galactose 

d-Allose 

to 

to 

i-Mucic  acid 

i-Allo-mucic  acid 

CHO 

CHO 

CHO 

CHO 

1 

1 

1 

1 

HO—  C—  H 

HO—  C—  H 

H—  C—  OH 

H—  C—  OH 

1 

1 

1 

1 

HO—  C—  H 

H—  C—  OH 

H—  C—  OH 

HO—  C—  H 

1 

I 

1 

1 

HO—  C—  H 

H—  C—  OH 

H—  C—  OH 

HO—  C—  H 

1 

1 

1 

I 

H—  C—  OH 

H—  C—  OH 

HO—  C—  H 

HO—  C—  H 

1 

1 

1 

1 

CH2OH 

CH2OH 

CH2OH 

CH2OH 

d-Talose 

d-Altrose 

1-Talose 

to 

to 

d-Talo-mucic  acid 

-Talo-mucic  acid 

MONO-SACCHAROSES  345 

It  would  be  out  of  place,  in  this  book,  to  discuss  in  detail  the  methods 
by  which  a  definite  configuration  has  been  assigned  to  each  known  aldo- 
hexose  and,  similarly,  to  each  known  stereo-isomer  of  the  tetrose, 
pentose  and  heptose  groups.  We  may  form  some  idea  of  how  it  is 
accomplished  by  recalling  the  following  transformations  that  are  pos- 
sible in  the  case  of  any  aldose  mono-saccharose,  (i)  By  oxidation, 
we  may  pass  to  the  corresponding  mono-basic  and  di-basic  acids,  as 
indicated  in  the  table  of  isomers  on  the  preceding  page;  (2)  by  reduction, 
to  the  poly-hydroxy  alcohols;  (3)  by  the  osazones  and  osones,from  an  aldose 
to  its  corresponding  ketose;  (4)  by  the  hydrcgen  cyanide  reaction,  to  the 
aldose  sugar  containing  one  more  carbon  atom;  and,  finally,  (5)  by  the 
oxime  reaction,  to  the  aldose  sugar  containing  one  less  carbon  atom.  By 
means  of  all  of  these  reactions  combined  it  has  been  possible  to  show 
definitely  the  relationship  in  configuration  between  all  known  sugars 
of  whatever  carbon  content  whether  aldose  or  ketose  in  structure. 

It  must  be  emphasized,  that  the  designations  d-,  dextro  and  /- 
lew  for  the  stereo-isomers,  refers  wholly  to  their  configuration  in  space 
and  has  no  reference  to  the  optical  activity,  so  far  as  the  direction  of  the 
rotation  is  concerned,  for  this  may  be  the  same  or  different.  This  is 
illustrated  by  the  fact  that  d-glucose,  which  itself  is  dextro  rotatory, 
by  means  of  its  osazone  and  osone,  is  converted  into  the  corresponding 
ketose  sugar  which,  therefore,  must  be  the  dextro  form  of  fructose.  It 
is,  however,  lew  in  the  direction  of  its  optical  rotation,  i.e.,  d-/ructose 
is  lew-rotatory. 

Lactone  Constitution  of  Glucose 

In  discussing  the  aldehyde  and  ketone  constitution  of  the  mono- 
saccharoses  we  stated  that  while  this  constitution  holds  for  the  com- 
pounds as  they  react  in  water  solution  it  is  not  the  constitution  at  present 
accepted  for  the  actual  substances  themselves. 

Muta-rotation. — Two  facts  have  led  to  an  advancement  in  our 
ideas  as  to  the  constitution  of  the  carbohydrates,  especially  of  glucose. 
The  first  fact  is  that  a  solution  of  glucose  changes  in  its  optical  rotatory 
power,  being  nearly  twice  as  great  when  the  solution  is  freshly  prepared 
as  it  is  when  the  solution  has  stood  for  some  time.  This  changing  of 
rotatory  power  has  been  termed  muta-rotation.  The  muta-rotation  of 
glucose  has  been  understood  only  in  connection  with  a  constitution 
which  makes  possible  the  existence  of  two  isomeric  forms  possessing 


346  ORGANIC  CHEMISTRY 

different  rotatory  power  and  which  exist  together  under  a  changing 
condition  of  equilibrium. 

Alpha-  and  Beta-Methyl  Glucosides. — The  second  fact  which 
brought  about  a  change  in  our  ideas  as  to  the  constitution  of  glucose  is 
that  there  have  been  shown  to  exist  two  isomeric  methyl  ethers  de- 
rived from  d-glucose.  We  have  spoken  of  only  one  class  of  de- 
rivatives of  the  mono-saccharoses,  viz.,  the  esters  resulting  from  the 
reaction  of  the  alcoholic  hydroxyl  groups  with  an  acid  chloride  or  acid 
anhydride.  As  alcohols,  however,  the  mono-saccharoses  form  both 
potassium  salts  or  alcoholates  analogous  to  potassium  ethylate,  C2H5OK, 
and  they  also  form  ethers  analogous  to  methyl  or  ethyl  ether.  When 
glucose  (d-glucose)  is  dissolved  in  methyl  alcohol  and  the  solution 
treated  with  dry  hydrochloric  acid  gas  a  methyl  ether  of  glucose  is 
formed.  This  methyl  ether  which  is  known  as  methyl  glucoside  exists 
in  two  isomeric  forms  distinguished  as  a-methyl  glucoside  and  /?- 
methyl  glucoside.  They  were  discovered  by  Emil  Fischer  in  1893 
and  are  considered  analogous  to  the  natural  glucosides. 

Alpha  and  Beta  Glucoses. — From  the  two  isomeric  methyl  glucosides 
Armstrong  obtained  two  isomeric  glucoses.  a-Methyl  glucoside  is 
hydrolyzed  by  the  action  of  the  enzyme  maltase  and  when  so  hydrolyzed 
a-glucose  is  obtained.  Similarly  /?-methyl  glucoside  hydrolyzed  by 
emulsin  yields  0-glucose.  The  two  isomeric  forms  of  glucose  are  readily 
transformed  into  each  other  and  exist  together  in  equilibrium  but  by 
controlling  the  conditions  each  of  the  forms  has  been  obtained  and 
studied.  The  methyl  glucosides  differ  from  glucose  in  not  reacting  with 
either  Fehling's  solution  or  with  phenyl  hydrazine  and  in  not  exhibiting 
muta-rotation.  The  optical  rotation  of  the  glucosides  and  the  glucoses 
is  as  follows : 

a-Methyl glucoside, m.p.  165° («)D  =  +  157°    a-Glucose  («)„  =  +  105° 
0-Methyl glucoside,  m.p.  104°  («)D  =  —  33°      0-Glucose  (a)D  =  +  22° 

Lactone  Formula. — What  now  is  the  accepted  constitution  of  these 
glucosides  and  of  glucose  and  how  does  it  explain  the  existence  of  two 
isomeric  forms  of  each  and  also  the  muta-rotation  of  glucose?  As 
early  as  1883  Tollens  suggested  another  constitution  than  the  aldehyde- 
alcohol  one  for  glucose  because  the  compound  is  not  as  reactive  as  such 
a  constitution  would  indicate.  He  suggested  that  four  of  the  carbon 
atoms  in  the  hexose  chain  were  linked  by  an  oxygen  atom  into  a  ring. 
If  we  examine  the  formula  of  glucose  as  given  for  the  aldehyde  consti- 


MONO-SACCHAROSES 


347 


tution  we  see  that  in  any  such  poly-hydroxy  compound  there  is  the 
possibility  of  the  formation  of  a  gamma-lactone  ring  similar  to  the  lac- 
tones  formed  from  the  gamma-hydroxy  acids  (p.  243).  The  two  formu- 
las are  as  follows: 

H— C  =  O  H— C— OH 


H—  C—  OH 

H-C-OH 

HO—  ( 

:—  H 

HO—  ( 

:—  H 

H—  ( 

:—  OH 

H—  ( 

j><^ 

H—  ( 

:—  OH 

H—  ( 

::—  OH 

H—  C—  OH 

1 

H—  ( 

C—  OH 

I 
H 

Aldehyde  Formula 

H 

Y-Lactone  Formul 

(Y-oxide) 

d-Glucose 

Such  a  lactone  would  be  the  anhydride  of  a  compound  containing 
two  hydroxyl  groups  linked  to  one  carbon  atom.  A  compound  of 
this  character  would  also  be  able  to  lose  water  in  another  way  as 
discussed  in  connection  with  aldehyde  (p.  115)  yielding  a  product  of 
the  aldehyde  constitution  as  follows: 

OH  H—  C  =  O 


H— C-OH 


H-  C— OH 


— H2O      H— C— OH    — H2O     HO— C— H 


+  H2O  HO— C— H       +H2O        H— C— OH 


CH.OH 

Glucose 

Laclone  formula 


H— C— OH 
H— C— OH 


CH2OH 

Aldehydrol 
Hydrated 
Product 


H— C— OH 


CH2OH 

Glucose 

Aldehyde  formula 


348 


ORGANIC  CHEMISTRY 


This  explains  what  takes  place  when  glucose  in  water  solution  acts 
as  an  aldehyde  toward  phenyl  hydrazine  and  other  reagents.  When 
put  into  water  solution  a  small  amount  of  the  glucose  of  the  lactone 
constitution  is  converted  into  the  hydrated  produce  called  aldehydrol. 
Under  the  influence  of  the  reagent,  phenyl  hydrazine,  the  aldehydrol 
loses  water  yielding  the  aldehyde  which  is  then  removed  by  reaction 
with  the  reagent.  This  results  in  another  portion  of  the  lactone 
being  converted  into  the  aldehydrol  and  this  to  the  aldehyde  and  so  on 
until  all  of  the  glucose  is  converted  into  the  aldehyde  and  reacted  upon 
by  the  phenyl  hydrazine.  In  water  solution  without  the  phenyl 
hydrazine  the  lactone  and  the  aldehydrol  exist  in  equilibrium  the  reac- 
tion with  water  being  reversible. 

Explanation  of  Isomeric  Glucoses  and  Glucosides. — As  the  lactone 
constitution  fixes  the  position  of  the  hydrogen  and  hydroxyl  which  are 
linked  to  the  end  carbon  atom  of  the  lactone  ring  stereo-isomerism  of 
the  geometric  type  is  possible.  The  two  isomeric  glucoses  and  the  two 
isomeric  methyl  glucosides  are  thus  represented  as  follows: 


CH2OH 

o-Glucose 

(a)D   =    +   105° 


CH2OH 

0-Glucose 

(a)D    =    +   22° 


H— C— OCH3 


HO— C— H 


MONO-SACCHAROSES 

H3CO— C-H 


HO— C— H 


349 


CH2OH 

a-Methyl  Glucoside 

(a)D  =    +  157° 
m.p.  =  165° 


CH2OH 

/3-Methyl  Glucoside 

(»)D  =  -  33° 

m.p.  =  194° 


That  both  of  the  glucoses  and  also  both  of  the  methyl  glucosides  have 
been  prepared  and  their  relationship  to  each  other  established  supports 
the  theory  of  the  lactone  constitution. 

Explanation  of  Muta  Rotation. — That  glucose  in  water  solution 
undergoes  a  rapid  change  in  its  optical  rotation  is  explained  by  the  easy 
conversion  of  the  two  isomeric  glucoses  into  each  other.  Starting  with 
(a) -glucose  when  it  goes  into  solution  some  hydration  occurs  and  the 
aldehydrol  is  formed.  The  reaction  being  reversible  glucose  is  reformed 
but  in  reforming  the  lactone  either  the  alpha  or  the  beta  form  is  possible 
and  some  beta  results.  The  formation  of  the  beta  isomer  effects  a 
change  in  the  optical  rotation.  This  continues  until  equilibrium  is 
established  when  the  optical  rotation  remains  constant  but  is  different 
from  that  which  it  was  at  the  beginning  when  the  glucose  was  first 
dissolved. 

Oxonium  Compound. — The  transformation  of  alpha  and  beta  glu- 
coses into  each  other  resulting  in  muta-rotation  has  also  been  explained 
by  Armstrong  in  another  way  than  through  the  intermediate  aldehydrol 
compound.  According  to  this  author  the  hydration  of  the  lactone  form 
of  glucose  results  in  the  formation  of  an  oxonium  compound  in  which 
oxygen  is  tetra-valent.  The  loss  of  water  from  this  oxonium  compound 
restores  the  lactone  constitution  but  in  returning  to  the  lactone  either 
the  alpha  or  beta  form  may  result. 


CH2OH 

or-Glucose 


CHoOH 

Oxonium  Compound 


CH2OH 

0-Glucose 


In  the  loss  of  water  from  the  oxonium  compound  an  imsaturated 
intermediate  product  is  formed  by  the  hydrogen  and  hydroxyl  being 
taken  one  from  the  oxonium  group  the  other  from  the  carbon  atom  at 
the  end  of  the  lactone  ring.  The  saturated  lactone  is  then  formed  from 
this  intermediate  unsaturated  compound  by  a  shifting  of  the  oxonium 
hydrogen  atom  to  the  neighboring  carbon  atom. 

Further  details  of  these  transformations  of  the  isomeric  glucoses 
and  methyl  glucosides  and  other  facts  in  support  of  the  lactone  consti- 
tution of  glucose  must  necessarily  be  omitted  from  our  study  though 
they  are  essential  to  a  full  understanding  of  the  matter.  For  such 
fuller  discussion  such  works  as  Armstrong  and  Cohen  may  be  consulted. 
We  may  simply  add  that  recent  work  by  Nef  and  his  pupils  not  only 
supports  the  lactone  constitution  but  shows  that  both  alpha-lactones 


MONO-SACCHAROSES  351 

and  beta-lactones  as  well  as  gamma -lactones  are  possible  in  the  case  of 
the  glucoses. 

We  may  now  take  up  the  consideration  of  the  individual  carbohy- 
drates following  the  order  of  our  classification,  viz.,  (i)  Mono-saccha- 
roses, (2)  Di-saccharoses,  or  poly-saccharoses  that  are  true  sugars,  and 
(3)  Poly-saccharoses,  or  poly-saccharoses  that  are  not  true  sugars. 

Glucose,  Dextrose,  Grape  Sugar 

Of  the  hexose  monosaccharoses  only  two  of  the  fourteen  known  aldo- 
hexoses  need  to  be  described  in  detail  and  only  one  keto-hexose.  The 
most  important  hexose  sugar  is  glucose.  As  it  is  also  dextro-rotatory 
toward  polarized  light,  it  is  known  as  dextrose.  This  sugar  is  very 
widely  distributed  in  nature,  being  found  in  the  juice  of  most  sweet 
fruits,  especially  in  grapes.  On  account  of  this  last  fact  it  is  known  also 
as  grape-sugar.  The  three  names,  therefore,  viz.,  glucose,  dextrose, 
and  grape-sugar,  all  apply  to  the  same  chemical  compound.  We  shall 
use  the  name  glucose  in  preference  to  dextrose  except  in  particular 
cases.  It  is  also  found  in  certain  roots,  leaves  and  flowers  and  in 
human  urine  in  the  pathological  condition  known  as  diabetes.  It  is 
a  normal  constituent  of  human  blood  where  it  is  present  to  the 
amount  of  o.i  per  cent.  It  may  be  prepared  by  the  hydrolysis  of 
starch  or  cane  sugar  the  former  being  the  commercial  source.  Corn 
syrups  are  made  by  hydrolyzing  corn  starch  and  are  composed  largely 
of  glucose.  Glucose  crystallizes  from  alcohol,  or  from  concentrated 
water  solution,  in  anhydrous  needles  which  melt  at  146°.  It  also 
forms  crystals  with  one  molecule  of  water  of  crystallization.  It  is 
easily  soluble  in  water,  or  in  dilute  alcohol,  but  practically  insoluble 
in  absolute  alcohol.  It  is  optically  active,  being  dextro  rotatory, 
(CK)D  =  4~  53°  at  2O°C.  It  reduces  Fehling's  solution  and  is  fermented 
by  yeast  zymase  with  the  formation  of  alcohol.  Its  osazone  crystal- 
lizes in  tufts  of  thin  needles.  In  its  space  configuration  it  is  d-glucose. 
The  1-glucose  and  the  i-glucose  (racemic  form)  are  also  known. 

Galactose 

The  other  aldo-hexose  which  we  shall  mention  is  galactose.  This 
sugar  is  stereo-isomeric  with  d-glucose.  The  two  having  the  respec- 
tive configurations  as  given  in  the  table,  p.  344.  It  is  obtained  by  the 


352  ORGANIC  CHEMISTRY 

hydrolysis  of  milk-sugar,  or  lactose.  It  crystallizes  in  microscopic 
hexahedra  which  melt  at  168°.  It  reduces  Fehlings  solution  and  is 
fermentable  by  yeast  zymase.  It  also  yields  an  osazone. 

Fructose,  Levulose,  Fruit  Sugar 

The  remaining  hexose,  which  we  shall  mention,  is  a  keto-hexose. 
It  is  structurally  isomeric  with  glucose.  Because  it  is  found  widely 
distributed  in  fruits,  where  it  is  usually  associated  with  glucose,  it  is 
known  as  fructose,  and  also  as  fruit-sugar.  It  is  found  in  honey  and  is 
also  obtained  by  the  hydrolysis  of  a  poly-saccharose  known  as  inulin 
which  is  found  in  Dahlia  tubers.  It  is  optically  active  being  lew- 
rotatory,  the  opposite  of  glucose,  (a)D  =  —92°  at  2O°C.  Because  it  is 
levo-rotatory  it  is  also  known  as  levulose.  The  three  names,  therefore, 
viz.,  fructose,  levulose  and  fruit-sugar,  correspond  to  the  three  similar 
names  for  glucose.  It  is  known  in  the  three  stereo-chemical  forms 
of  d-,  /-,  and  i-,  and  these  three  forms  are  all  structurally  isomeric 
with  the  three  similar  forms  of  d-glucose.  As  stated  before  it  corre- 
sponds, in  configuration  to  d-glucose  and  is  therefore  stereo-chemically 
d-fructose.  When  glycerose  is  condensed,  or  polymerized,  to  a  hexose 
sugar,  it  is  the  i-fructose,  also  known  as  a-acrose,  which  is  formed. 
This  was  the  first  hexose  sugar  to  be  prepared  synthetically.  Fructose 
crystallizes  with  difficulty  from  alcohol  in  water  free  crystals.  From 
water  it  crystallizes  with  ^  molecule  of  water  of  crystallization.  It 
reduces  Fehling's  solution  and  undergoes  alcoholic  fermentation  with 
yeast  zymase.  It  yields  the  same  osazone  as  glucose. 

Invert  Sugar.  Inversion. — We  have  mentioned  the  fact  that 
glucose  may  be  obtained  by  the  hydrolysis  of  cane-sugar.  In  this 
hydrolysis  not  only  glucose  but  also  fructose  is  obtained.  Cane  sugar 
is  a  di-saccharose  of  the  composition  Ci2H22On.  When  it  is  hydrolyzed 
it  splits  and  is  converted  into  two  molecules  of  mono-saccharoses. 
One  of  these  molecules  is  glucose  and  the  other  is  fructose. 

Ci2H22On          +          H2O        >        C6H12O6          +          C6H12O6 

Cane  Sugar,  Glucose,  Dexlro.  Fructose 

Dextro                                                                                   va)D  =  +  53°                                         Lcvo 
(a)D  =  +  66°  (,a)D 92° 


Invert  Sugar.   Levo 
(a)D  =   -  39° 


As  the  glucose  is  dextro  rotatory,  with  a  value  of  +53°,  while  levulose 
is  lew  rotatory ,  with  a  value  of  —  92°,  it  is  plain  that  the  mixture  of  equal 


DI-SACCHAROSES  353 

molecules  of  each  must  be  lew-rotatory,  with  a  value  of  -39°.  As  we 
shall  find  later,  cane  sugar  is  also  optically  active,  being  dextro  rotatory, 
with  a  specific  rotation  (a)D  =  +66°.  When,  therefore,  a  molecule  of 
cane  sugar  is  hydrolyzed,  with  the  formation  of  equal  molecules  of  glu- 
cose and  fructose,  the  rotation,  which,  in  the  original  cane  sugar,  is  dextro, 
is  changed  to  lew  or,  as  we  say,  is  inverted.  The  mixture  of  equal  mole- 
cules of  glucose  and  fructose  which  is  thus  obtained  is  termed  invert 
sugar  and  this  particular  hydrolytic  process  is  called  inversion.  Invert 
sugar  is  thus  formed  whenever  cane  sugar  is  hydrolyzed.  It  is  present 
in  honey,  which  is  the  chief  natural  source. 

B.  DI-SACCHAROSES.     Ci2H22On 

The  group  of  di-saccharoses,  or  poly -saccharoses  which  are  true 
sugars,  includes  three  common  and  important  members,  (i)  Cane 
sugar,  or  sucrose,  perhaps  the  most  important  of  all  the  carbohydrates, 
unless  that  position  may  be  disputed  by  starch  a  poly-saccharose.  (2) 
Malt  sugar,  or  maltose,  found  in  malt.  (3)  Milk  sugar,  or  lactose,  the 
sugar  present  in  milk. 

Sucrose,  Cane  Sugar 

Sucrose,  or  cane  sugar,  as  it  is  called,  because  it  was  formerly 
obtained  almost  exclusively  from  the  juice  of  the  sugar  cane,  is  found 
widely  distributed  in  nature.  The  chief  sources  from  which  it  is  now 
obtained  industrially,  are,  (i)  sugar  cane,  (2)  sugar  beet,  (3)  sorghum 
cane,  (4)  maple  sap.  It  occurs  in  smaller  amounts,  not  sufficient  for 
commercial  uses  in  most  plants  associated,  usually,  with  glucose  or 
fructose  or  both.  Sucrose  is  easily  soluble  in  water  but  only  slightly 
so  in  dilute  alcohol.  It  separates  from  water  solution  in  beautiful 
mono-clinic  crystals  and  is  much  more  easily  crystallized  than  the 
hexose  sugars.  It  is  optically  active,  being  dextro  rotatory,  (o:)D  = 
+  66°.  It  does  not  form  osazones  withphenyl  hydrazine,  does  not  reduce 
Fehling's  solution,  and  is  not  fermentable  with  yeast  zymase,  nor  does  it 
react  with  hydrogen  cyanide.  It  may  be  hydrolyzed  by  means  of 
dilute  acids  or  by  means  of  certain  enzymes,  viz.,  sucrase,  or  invertase. 
The  products  of  such  hydrolysis  are  glucose  and  fructose  as  has  just 
been  described.  It  forms  salts  with  some  bases,  e.g.,  calcium  or  stron- 
tium hydroxides.  These  salts  are  known  as  sucrates. 

Constitution  of  Sucrose. — Both  the  composition  of  sucrose,  and  its 

23 


354  ORGANIC  CHEMISTRY 

hydrolysis  into  two  molecules  of  hexose,  show  that  it  must  be  the 
anhydride  of  two  molecules  of  hexose  sugar. 

+  H20 
Ci2H22On      ;ZH      2C6H12O6 

-H2O 

Also  the  two  molecules  of  hexose  from  which  sucrose  may  be  con- 
sidered as  being  formed  are,  one  an  aldo-hexose,  and  the  other  a  keto- 
hexose.  Its  non-activity  toward  Fehling's  solution,  phenyl  hydrazine, 
and  hydrogen  cyanide,  indicates  that  in  the  sucrose  molecule  there  is 
no  aldehyde  or  ketone  group.  It  will  lead  us  too  far  to  discuss  the  reasons 
for  assigning  the  following  formula  which  agrees  with  the  properties  of 
the  compound  as  just  given. 

H  H 

C  =  0  CH2OH 

I  ! 

HO— C— H         O  =  C  HOC— H 

H— C— OH      H—  C— OH-H2O      \H— C— OH        /  H-C— OH 

I      +       I  J       o<       I 

HO— C— (H    HO— C— H  C— H  HO-C— H 

HO— C— H    HO)— C— H  HO— C— H  C— H 

CH2OH  CH2OH  CH2OH  CH2OH 

Glucose        Fructose  Sucrose 

Sources  and  Industrial  Processes. — The  industrial  process  of 
extracting  and  refining  sucrose  is  most  important.  The  sugar  industry 
is  one  of  the  big  industries  of  the  world  and  a  brief  statement  in  regard 
to  it  will  not  be  out  of  place.  The  amount  of  sucrose  present  in  various 
plants  may  be  given  as  follows : 

Sugar  cane,       15-20  per  cent 

Sugar  beet,         7-17  per  cent 

Sorghum  cane,    7-12  per  cent 

Maple  sap,          2-  3  per  cent  (  as  much  as 

Maize  stalks,          14  per  cent  |  12  per  cent  of 

Pine  apples,  n  per  cent  I  this  is  invert  sugar. 

Strawberries,      5-  6  per  cent 


DI-SACCHAROSES  355 

Only  the  first  two  of  these  sources  are  industrially  important  so  far 
as  obtaining  the  sugar  in  a  commercial  form  is  concerned. 

We  shall  follow  the  process  as  it  is  carried  out  with  sugar  beets 
though,  in  general,  it  is  the  same,  or  similar,  when  the  sugar  is  obtained 
from  the  sugar  cane.  There  are  three  general  stages  in  the  process. 

1.  Extraction  of  the  juice. 

2.  Concentration  of  the  juice  and  crystallization  of  the  sugar. 

3.  Refining  of  the  sugar. 

Extraction  of  Juice. — Originally  the  cane  or  beets  were  macerated 
by  rolling  or  cutting  and  then  the  macerated  mass  pressed  to  remove 
the  juice.  Where  the  process  is  not  perfected  only  about  40-60  per 
cent  of  the  sugar  present  in  the  cane  is  extracted.  Cane  juice  so 
obtained  usually  contains  15-19  per  cent  sugar  and  beet  juice  20-25  Per 
cent.  After  the  first  pressing  the  extracted  mass  is  moistened  with 
water  and  a  second  pressing  is  sometimes  made.  By  an  improved 
process  of  extraction  by  pressure,  known  as  the  Steffen  process,  all  but 
about  2.5-5.0  per  cent,  sugar  is  obtained  from  beets. 

Diffusion  Process. — The  most  improved  process,  however,  for  ex- 
tracting the  sugar  from  both  cane  and  beets  is  known  as  the  diffusion 
process.  The  process  depends  upon  the  general  property  of  osmosis. 
Water,  at  70°,  to  an  amount  equal  to  1.2-1.5  times  the  weight  of  the 
beets,  is  added  to  the  sliced  beets.  The  action  is  carried  out  in  a  series 
of  compartments  and  by  diffusion  and  osmosis  the  sugar  is  almost 
completely  removed  from  the  beets.  Only  about  0.3-0.4  per  cent 
sugar  remains  in  the  residue.  In  the  case  of  sugar  cane  the  loss  of  sugar 
is  reduced  to  less  than  20  per  cent  of  the  original  amount,  i.e.  to  about 
3  per  cent  sugar.  The  disadvantage  of  the  diffusion  process  is  that  the 
use  of  so  much  water  increases  the  cost  of  the  concentration  of  the  juice. 
The  residue  left,  after  the  extraction  of  the  juice  is  known  as  bagasse, 
and  the  juice  as  it  is  first  obtained  is  termed  raw  juice.  The  bagasse  is 
used  as  cattle  food  or  it  is  dried  and  used  as  fuel  in  some  other  part  of 
the  process. 

Concentration. — The  next  stage  in  the  process  is  the  purification  and 
concentration  of  the  juice  and  the  crystallization  of  the  sugar.  The 
raw  juice  contains,  as  impurities,  pectins,  proteins  and  mineral  salts. 
These  are  usually  removed  by  the  addition  of  lime  at  85°-9o°,  which 
causes  the  precipitation  of  the  impurities.  Care  must  be  exercised 
however,  or  some  sugar  will  also  be  precipitated  in  the  form  of  calcium 


356  ORGANIC  CHEMISTRY 

sucrate.  As  an  excess  of  lime  is  unavoidable  it  is  necessary,  in  order  to 
prevent  the  precipitation  of  sugar,  to  pass  an  excess  of  carbon  dioxide 
into  the  solution.  This  removes  the  excess  of  lime  and  at  the  same  time 
sets  free  any  sugar  combined  as  sucrate.  The  liquid  is  then  filtered 
and  the  treatment  with  carbon  dioxide  repeated  a  second  and  third 
time  at  95°  and  100°,  respectively.  The  third  treatment  is  sometimes 
made  with  sulphur  dioxide  which  decolorizes  as  well  as  purifies  the 
solution.  This  whole  treatment  with  lime  and  carbon  dioxide  must  be 
carefully  watched  or  much  loss  will  occur.  After  the  final  saturation 
with  gas  the  purified  solution  is  boiled  and  filtered  when  it  is  ready  for 
concentration. 

Evaporation. — The  purified  juice  is  clear  pale  yellow  and  contains 
from  lo-n  per  cent  of  sugar.  The  concentration  of  this  juice  is 
usually  accomplished  by  evaporation  with  steam  coils  placed  directly 
in  the  liquid.  This  evaporation  is  carried  out  in  pans  from  which  the 
air  has  been  more  or  less  exhausted,  known  as  -vacuum  pans.  They  are 
arranged  in  multiple  batteries  so  that  the  steam  from  the  one  containing 
the  more  concentrated  juice  helps  to  boil  the  next  one  containing  less 
concentrated  juice.  The  exhaustion,  or  vacuum,  in  the  pan  containing 
the  fresh  juice,  where  it  is  the  highest,  reaches  640  mm.  mercury,  and 
in  the  pan  containing  the  most  concentrated  juice  the  vacuum  is  about 
150  mm.  The  temperature  of  boiling  in  the  pans  ranges  from  56°, 
in  the  pan  with  the  highest  vacuum,  i.e.  the  pan  containing  the  fresh 
juice,  to  94°  in  the  pan  with  the  lowest  vacuum,  i.e.  the  pan  containing 
the  most  concentrated  juice. 

Crystallization. — After  concentration  the  juice  is  dark  brown  in 
color  and  contains  50-55  per  cent  sugar.  To  bring  about  crystalliza- 
tion the  juice  must  be  filtered  and  then  further  evaporated  in  simple 
vacuum  pans  until  the  concentration  of  the  juice  is  about  85  per  cent 
sugar.  The  crystallization  begins  upon  the  steam  coil  tubes  and  when 
this  crystallization  reaches  a  certain  point  the  hot  solution,  containing 
considerable  crystalline  sugar,  is  discharged  from  the  pan  into  tanks  with 
stirrers.  This  crystalline  liquid  mass  is  called  massecuite.  This  masse- 
cuite  is  allowed  to  cool  when  it  becomes  practically  a  solid  mass  of 
crystals  wet  with  liquid.  From  the  crystallization  tanks  the  massecuite 
is  passed  next  to  centrifuge  machines  in  which  the  liquid  is  thrown  off 
from  the  crystals.  The  crystalline  sugar  thus  obtained  is  a  more  or  less 
dark  colored  mass,  depending  on  whether  any  water  or  sugar  solution 


DI-SACCHAROSES  357 

was  used  for  washing  in  the  centrifuge.  This  first  crystalline  product  is 
known  as  first  product  sugar  and  the  liquid  thrown  off  is  known  as 
molasses.  The  entire  process  of  evaporation  and  crystallization  is 
repeated  with  the  molasses.  From  this  second  process  a  second  mas- 
secuite,  a  second  product  sugar  and  a  second  molasses  are  obtained. 
From  this  second  molasses  more  sugar  may  still  be  obtained  by  means  of 
a  lime  or  strontia  process,  but  this  is  not  always  done.  The  molasses 
obtained  from  beet  juice  amounts  to  only  about  1.3  per  cent  and  contains 
about  40-50  per  cent  sugar.  The  sugar  present  in  this  molasses, 
though  so  high  in  percentage  amount,  does  not  crystallize  because  the 
molasses  contains  8-10  per  cent  of  mineral  salts.  The  presence  of 
these  mineral  salts  prevents  the  crystallization  of  five  times  their  weight 
of  sugar.  The  molasses  also  contains  about  i  .'5  per  cent  of  invert  sugar. 
The  first  and  second  product  sugars  are  now  ready  for  refining. 

Refining. — The  combined  first  and  second  product  sugars  are  called 
raw  sugar,  and  contain  88-96  per  cent  sugar.  The  refining  of  this 
raw  sugar  consists,  essentially,  in  re-solution,  purification  and  de- 
coloration, evaporation  and  crystallization.  The  purification  is  usually 
accomplished  by  decolorizing  with  animal  charcoal  and  filtering.  So- 
dium thio-sulphate  is  sometimes  used  as  a  decolorizer.  To  destroy 
the  last  traces  of  yellow  color,  a  very  small  amount  of  ultra-marine 
blue  was  formerly  added.  As  a  result  of  all  these  treatments  the 
crystalline  sugar  finally  obtained  is  pure  white  granulated  sugar. 

History  and  Statistics. — A  few  facts  of  history  and  statistics  may  be 
of  interest.  The  first  sugar  material  used  was,  probably,  honey,  con- 
taining, as  previously  stated,  invert  sugar.  The  sugar  cane  has  been 
known  since  ancient  times  in  China,  India,  Egypt,  Greece,  etc.  Sugar 
was  a  commercial  substance  in  the  seventh  century.  The  culture  of 
the  sugar  cane  was  introduced  into  Brazil  and  the  West  Indies  in  the 
fifteenth  century.  At  the  present  time  it  is  grown  in  Cuba,  Philippine 
Islands,  Jamaica,  Louisiana,  Brazil,  Peru,  China,  Japan,  India,  Egypt 
and  Australia.  The  extraction  of  sugar  from  beets  was  first  accom 
plished  commercially  at  the  very  beginning  of  the  nineteenth  century* 
but  only  about  3  per  cent  of  the  sugar  was  obtained.  Except  for  a 
short  time,  viz.,  from  1806-1814,  when  Europe  was  closed  to  the  im- 
portation of  cane  sugar,  it  was  not  successfully  prepared  until  about 
1828  in  France  and  1836  in  Germany.  In  1865  one  and  one-half  mil- 
lion tons  were  produced.  In  1866  beet  sugar  was  only  30  per  cent  of 


35$  ORGANIC  CHEMISTRY 

a  total  sugar  production  of  three  million  tons.  In  1887  it  was  47  per 
cent  of  five  million  tons.  In  1899  it  was  64  per  cent  of  seven  and  one- 
half  million  tons.  In  1901  it  was  67  per  cent  of  nine  million  tons.  In 
1910  it  was  46.5  per  cent  of  fifteen  million  tons.  In  the  United  States 
sugar  cane  is  grown,  chiefly,  in  Louisiana,  and  the  Philippine  Islands. 
The  sugar  beet,  chiefly,  in  Michigan,  Wisconsin,  Colorado,  Kansas 
and  Nebraska.  In  the  United  States  there  has  usually  been  a  tax 
upon  the  importation  of  refined  sugar  but  no  tax  upon  the  impor- 
tation of  raw  sugar,  containing  less  than  a  certain  per  cent  of  pure 
sugar.  Thus,  in  this  country  sugar  is  imported  as  raw  sugar  and  re- 
fined after  importation.  On  account  of  the  above  statement  in  regard 
to  the  tax  upon  sugar,  it  is  necessary  to  determine  accurately,  the 
amount  of  pure  sugar  in  raw  sugar. 

Analysis. — The  analysis  of  sugar  is  carried  on,  almost  entirely,  by 
the  use  of  the  polariscope.  As  sucrose  has  a  definite  optical  rotation  the 
determination  of  the  rotation  of  a  sugar  solution  gives  us  a  means  of 
accurately  determining  the  amount  of  pure  sucrose  in  any  sugar  solu- 
tion or  sugar  material. 

Polariscopes  used  for  this  particular  purpose  are  called  sacchari- 
meters,  and  the  scale  indicating  the  angle  of  rotation  is  graduated  so  as 
to  read,  per  cent  sugar  instead  of  degrees  rotation.  In  the  ordinary 
analysis  of  plants  and  food  materials  which  contain  more  or  less  su- 
crose the  sugar  is  usually  determined  by  the  precipitation  method  with 
Fehling's  solution,  after  first  hydrolyzing  the  sucrose  to  invert  sugar. 
This  method  gives  us,  of  course,  the  amount  of  invert  sugar  but  this 
may  readily  be  calculated  back  to  the  equivalent  amount  of  sucrose. 
The  sucrose  content  of  solutions  which  are  free  from  other  substances 
may  also  be  calculated  from  the  specific  gravity.  The  ordinary  forms 
of  immersion  spindle  hydrometer  specially  graduated  to  read  per  cent 
sugar  are  known  as  saccharometers.  The  special  form  most  commonly 
'  used  in  sugar  work  is  known  as  a  Brix  hydrometer  or  saccharometer,  and 
the  term  degrees  Brix  means  per  cent  sugar. 

Lactose,  Milk  Sugar 

The  second  important  di-saccharose  is  the  sugar  which  is  present  in 
milk  and  on  that  account  is  known  as  lactose  and  also  as  milk  sugar. 
The  amount  of  lactose  present  in  milk  is  about  3-6  per  cent.  It 
crystallizes  in  large  white  crystals  containing  one  molecule  of  water, 
which  it  loses  at  130°.  The  anhydrous  sugar  melts  at  about  200°.  It 


.  DI-SACCHAROSES 


359 


is  soluble  in  water  and  is  optically  active,  being  dextro  rotatory,  (a)D 
=  +52.5°.  It  is  not  fermented  by  yeast  zymase  and  it  yields  an 
osazone  of  very  fine  needle  crystals.  Lactose  differs  from  sucrose  in 
an  important  point,  viz.,  it  reduces  Fehling's  solution.  It  must,  there- 
fore, have  the  constitution  of  either  an  aldehyde  or  ketone  compound. 
On  hydrolysis  it  splits  and  yields  two  molecules  of  hexose  sugar,  one 
of  the  molecules  being  glucose  and  the  other  galactose.  As  galactose, 
according  to  the  formulas  given  on  page  344,  is  also  an  aldo-hexose, 
like  glucose  the  formula  for  lactose,  being  the  anhydride  of  these  two 
hexose  molecules,  would  probably  contain  an  aldehyde  and  not  a 
ketone  group.  Also  as  all  three  of  these  sugars  are  dextro  rotatory 
there  is  no  inversion  when  lactose  is  hydrolyzed. 

C12H22Ou    +    H20        >        C6H1206    +    C6H1206 

Lactose  (</)  Glucose  (rf)  Galactose  (d) 

The  full  constitutional  formula  for  lactose  is  similar  to  that  of  suc- 
rose but  contains  one  aldehyde  group. 
CH2OH  CH2(OH 


HO— C— H 


HO— C— H 


H)O— C— H 

H— C— OH 
HO— C— H 


H— C— OH 
H— C— OH 
HO— C— H 


— H20 


CHO 

Glucose 


CHO 

Galactose 


HO— C— H 
-C— H 


0 


O 


H—  C—  OH 


HO—  C—  H 


HO— C— H 

I 
H— C— OH 

I 
H— C— OH 

HO— C— H 


Lactose 


360  ORGANIC  CHEMISTRY 

Maltose,  Malt  Sugar 

Malt.  —  The  third  important  di-saccharose  is  maltose,  or  malt  sugar, 
which,  as  its  name  indicates,  is  found  in  malt.  Malt  is  the  sprouted 
grain  of  barley  or  any  other  cereal.  Usually  the  name  malt  applies  to 
that  obtained  from  barley.  When  these  grains  sprout  an  enzyme  known 
as  diastase,  converts  the  starch  of  the  grain  into  maltose.  The  action 
is  one  of  hydrolysis  and  will  be  discussed  again  under  starch.  The  malted 
grain  is  extracted  with  water  and  the  maltose  which  is  held  in  solution 
in  the  water  is  obtained  by  the  evaporation  of  the  water  and  the  crystal- 
lization of  the  sugar.  Maltose  is  also  obtained  as  a  thick  syrup.  The 
sugar  is  easily  soluble  in  water  and  crystallizes  in  fine  white  needles  con- 
taining one  molecule  of  water,  which  is  lost  at  100°.  It  is  optically 
active,  being  dextro  rotatory  like  glucose,  lactose  and  sucrose.  Its  speci 
fie  rotation  is  considerably  higher  than  the  other  sugars,  (a)D  =  +  137°- 
When  maltose  is  hydrolyzed  by  the  action  of  acids  or  the  enzyme,  mal- 
tase,  it  splits  into  two  molecules  of  hexose  sugar,  exactly  as  the  other 
two  disaccharoses,  but  the  product  of  the  hydrolysis  is  glucose  alone, 
i.e.,  one  molecule  of  maltose  yields  two  molecules  of  glucose.  In  this 
hydrolysis  there  is  no  inversion. 


Ci2H22On  -f-  H^O         -  >         CeH^Oe  -f~  CeH^Oe 

Maltose  (d)  Glucose  (d)        Glucose  (d) 

Maltose  reduces  Fehling's  solution  and  therefore  probably  contains 
an  aldehyde  group.  The  constitutional  formula  is  probably  the  same 
as  that  given  for  lactose.  It  yields  an  osazone  which  crystallizes  in 
tufts  of  needles  which  are  more  blunt  than  the  crystals  of  glucosazone. 
Maltose,  like  the  other  di-saccharoses  does  not  ferment  with  yeast 
zymase. 

Alcoholic  Fermentation.  —  The  statements,  just  made,  in  regard  to 
the  alcoholic  fermentation  of  the  di-saccharoses,  need  to  be  explained. 
Yeast,  i.e.,  ordinary  beer  yeast,  contains  several  enzymes.  The  definite 
enzyme  present  in  yeast,  and  which,  alone,  produces  alcoholic  fermen- 
tation of  sugars,  is  the  enzyme  zymase.  This  enzyme  -acts  only  upon 
the  hexoses  glucose,  fructose,  and  galactose.  It  has  no  action  upon 
either  of  the  three  di-saccharoses  we  have  mentioned.  When,  however, 
cane  sugar  or  malt  sugar  is  treated  with  ordinary  yeast  alcoholic  fer- 
mentation takes  place.  This  is  due  to  a  preliminary  action  of  other 
enzymes  upon  the  di-saccharoses  by  means  of  which  they  are  converted 
into  mono-saccharoses  and  then  the  mono-saccharoses  are  fermented 


POLY-SACCHAROSES  361 

by  the  yeast  zymase.  The  particular  enzyme  which  hydrolyzes  sucrose 
is  known  as  sucrase,  while  the  one  hydrolyzing  maltose  is,  maltase. 
Both  of  these  di-saccharose  hydrolyzing  enzymes  are  found  in  yeast  so 
that  yeast,  containing  a  mixture  of  several  enzymes,  will  ferment  the 
two  di-saccharoses  sucrose  and  maltose.  Lactose  is  wholly  unaffected 
by  yeast  because  the  lactose  hydrolyzing  enzyme,  lactase,  is  not  present 
in  yeast.  All  three  of  these  di-saccharoses  are  hydrolyzed  in  the  diges- 
tive tract  of  animals. 

C.  TRI-SACCHAROSES.     C18H32Oi6. 
Raflmose 

Only  one  tri-saccharose  is  important.  It  is  known  as  raffinose 
and  has  the  composition  Ci8H320]  6.  It  is  found  in  beets  and  is  present 
in  the  molasses  after  the  sucrose  sugar  is  crystallized  out.  It  is  also 
found  in  barley  and  in  cotton  seeds.  When  this  tri-saccharose  hydro- 
lyzes it  yields  first  a  di-saccharose  known  as  melibiose  and  a  mono- 
saccharose  fructose.  The  di-saccharose  is  then  further  hydrolyzed  and 
yields  two  molecules  of  mono-saccharose,  viz.,  glucose  and  galactose. 
The  complete  hydrolysis  of  the  tri-saccharose,  therefore,  is  as  follows, 


i6  +  2H20    K7*   C6H12O6  +  C6H1206  +  C6H12O6 

Raffinose  Fructose  Glucose  Galactose 

D.  POLY-SACCHAROSES,  (not  sugars).  (C6H]0O5)X. 

The  poly-saccharoses  which  are  not  true  sugars,  are  usually  called 
simply,  poly-saccharoses.  The  most  common  and  important  ones  are 
the  following, 

Starch,  widely  distributed  in  plants  as  reserve  food,  not  found  in 
animals. 

Cellulose,  widely  distributed  in  plants  as  the  fibrous  or  cell  wall 
substance. 

Glycogen,  present  in  the  liver  and  muscles  of  animals  ;  also  known  as 
animal  starch. 

Dextrin,  an  intermediate  hydrolytic  product  between  starch  and 
maltose;  sometimes  present  in  plants. 

Inulin,  similar  to  starch  and  found  in  certain  plants,  especially  in 
the  tubers  of  the  Dahlia. 

General  Character.  —  The  poly-saccharoses  are  compounds  made  up 
of  an  unknown  number  of  hexose  mono-saccharose  units.  The  com- 


362  ORGANIC  CHEMISTRY 

position  is  represented  by  the  formula,  C6H]oO5,  but  as  the  molecular 
mass  is  unknown,  it  is  written,  (C6HioO5)x.  On  hydrolysis  by  means  of 
acids  or  enzymes,  the  poly-saccharoses  all  yield  finally  hexose  mono- 
saccharoses,  as  follows, 

Starch  — >  Glucose 

Cellulose  — >  Mannose,  Galactose,  Glucose. 

Glycogen         >  Glucose 

Dextrin  >  Glucose 

Inulin  »  Fructose 

In  the  case  of  starch,  dextrin  and  probably  glycogen,  the  di-sac- 
charose,  maltose  is  an  intermediate  product  of  the  hydrolysis.  When 
hydrolyzed  by  enzymes  two  or  more  distinct  enzymes  are  necessary  to 
complete  the  hydrolysis  of  the  poly-saccharoses  to  mono-saccharoses. 
With  acids  the  hydrolysis  goes  through  to  the  final  product  though  the 
intermediate  products  are  probably  formed. 

Solubility. — The  poly-saccharoses  differ  from  the  sugars  in  the  ab- 
sence of  a  sweet  taste,  in  their  non-crystalline  character  and  in  their 
general  insolubility.  Inulin  and  dextrin  are  soluble  in  water,  glycogen 
is  soluble  to  an  opalescent  liquid,  while  starch  and  cellulose  are  in- 
soluble. In  hot  water  starch  forms  a  colloidal  solution  or  emulsion, 
known  as  starch  paste.  Starch  reacts  with  a  solution  of  iodine  and 
gives  a  beutifiul  blue  color.  This  is  a  characteristic  reaction  for  starch 
and  is  used  as  a  qualitative  test,  especially  in  microscopic  examination. 
Dextrin  exists  in  several  forms,  one  of  which  known  as  ery  thro -dextrin, 
gives  a  red  color  with  iodine. 

Iodine  Reaction. — The  other  forms  of  dextrin  known  as  achroo- 
dextrins,  give  no  color  with  iodine.  The  following  enzymes  act  upon 
the  different  poly-saccharoses  hydrolyzing  them  as  indicated: 

Enzymatic  Action. 

Starch      +  Diastase  — >     Dextrins       — >     Maltose. 

Dextrin    +  Diastase  — — »     Maltose 

Cellulose  +  Cellulase  >     Mannose  +  Galactose 

(Cytase) 

Glycogen  +  Glycogenase      >     Glucose 

Inulin       +  Inulase  — >     Fructose 

We  may  now  consider  a  few  facts  and  additional  properties  of  the 
individual  poly-saccharoses. 


POLY-SACCHAROSES  363 

Starch 

Photo-Synthesis. — With  the  exception  of  sucrose,  starch  is  prob- 
ably the  most  important  of  the  carbohydrates,  considered  as  a  food  or  in 
its  other  commercial  uses.  It  is  found  in  practically  all  green  plants 
and  is  a  reserve  food  material.  It,  therefore,  occurs  most  abundantly 
in  seeds,  roots,  tubers,  etc.  It  is  synthesized,  by  the  photo-synthetic 
process  in  the  leaves,  from  the  carbon  dioxide  in  the  air  and  water 
obtained  mostly  from  the  soil.  The  energy  for  this  synthesis  is  de- 
rived from  the  sun,  so  that  only  in  sun-light  is  the  synthesis  effected. 
Hence  the  process  is  termed  photo-synthesis.  The  active  substance  in 
the  leaves  which  effects  the  synthesis  is  chlorophyl,  or  green  coloring 
matter.  Thus  only  in  green  plants  is  this  photo-synthesis  brought 
about.  The  intermediate  products  of  the  synthetic  process  have  not 
been  established.  It  seems  probable  that  form -aldehyde  is  the  first 
compound  formed,  which,  by  condensation,  or  polymerization,  is 
converted  into  a  carbohydrate,  probably  glycerose,  which  again  maybe 
polymerized  into  fructose  (a-acrose)  and  glucose.  These  steps  have 
been  discussed  in  connection  with  the  consideration  of  the  triose, 
glycerose  and  also  in  connection  with  the  hexose  sugars,  glucose  and 
fructose.  From  glucose  starch  could  be  formed  by  condensation  with 
the  loss  of  water.  Whether  sucrose  is  formed  as  an  intermediate 
product  is  not  proven.  The  final  product,  of  photo-synthesis,  how- 
ever, is  starch.  After  thus  being  synthesized  in  the  leaves,  the  starch 
is  hydrolyzed  by  the  enzyme,  diastase,  present  in  the  leaves,  to 
maltose,  which  is  also  hydrolyzed  by  maltase,  likewise  present,  and 
the  final  product  of  these  hydrolyses  is  glucose. 

The  glucose,  thus  formed,  being  soluble,  is  transported  through  the 
plant  by  means  of  the  plant  sap  and  is  used  in  the  cells  as  energy  food. 
The  excess  of  glucose,  not  used  as  food,  is  again  converted  into  the 
form  of  starch  and  is  deposited  in  the  form  of  starch  grains  as  a  reserve 
food  material  in  the  reserve  organs  of  the  plant,  viz.,  seeds,  roots,  tubers, 
etc.  When  the  seed  germinates,  as  in  germinating  barley,  or  malt,  the 
same  enzymes,  diastase  and  maltase,  which  are  present  in  the  seed,  again 
hydrolyze  the  starch  into  glucose.  This  now  becomes  the  food  material 
for  the  growing  plantlet,  up  to  the  time  when,  by  the  development  of 
the  aerial  green  parts  of  the  plant,  it  becomes  able  to  synthesize  its 
own  food  material  from  the  carbon  dioxide  and  water  of  the  air  and  soil. 
In  this  hydrolysis  of  starch,  especially  in  the  seeds,  several  intermediate 


364  ORGANIC  CHEMISTRY 

products   have  been  isolated  or  proven  to  exist.     The  entire  action 
may  be  represented  as  follows, 

Starch    +    Diastase        >        Soluble  starch          — » 

Blue  with  I  Blue  with  I 

— ->    Erythro-dextrin.       — »    a-,  0-,  7-Archroo-dextrins.       — » 

Red  with  I  Colorless  with  I 

— >       Maltose    +    Maltase  — >       Glucose 

Di-saccharose  Hexose  Mono-saccharose 

Reduces  Fehling's  Reduces  Fehling's  Solution 

Solution 

By  the  action  of  acids  the  same  hydrolysis  is  effected,  though  all  of 
the  intermediate  products  have  not  been  isolated  or  proven. 

These  hydrolyses  indicate  that  starch  is  a  compound  existing  as  a 
complex  molecule  containing  numerous  mono-saccharose  groups  united 
in  an  anhydride  constitution,  similar  to  that  shown  to  exist  in  the  case 
of  the  di-saccharoses.  The  molecular  mass  of  starch  is  unknown,  but 
has  been  claimed  to  be  that  represented  by  the  formula, 

C2i6H36oOi8o  or  (C6Hi0O5)36    Starch 

Starch  is  present  in  plants  in  distinct  granular  form.  The  starch 
grains  from  different  plants  possess  characteristic  structures,  shown  by 
microscopic  examination,  e.g.,  potato  starch,  wheat  starch,  arrow-root 
starch,  etc.  These  starch  grains  are  wholly  insoluble  in  water.  When 
boiled  in  water  the  starch  grain  pellicles  break  and  the  starch  is  set  free 
in  such  a  form  that  it  produces  a  colloidal  solution  with  water.  This 
colloidal  solution  is  opalescent  and  is  known  as  starch  paste.  Both  in 
the  granular  form  and  in  the  starch  paste  the  starch  gives  the  blue  color 
reaction  with  iodine  solution.  Starch  paste  is  best  prepared  as  follows, 
Grind  up  about  one  gram  of  starch  with  just  sufficient  cold  water  to 
form  a  thin  mixture.  Boil  about  1000  c.c.  of  water  and  while  boiling 
add  the  starch  mixture  and  continue  to  boil  until  a  mucilaginous  paste 
is  formed.  Starch  paste,  so  made,  should  not  separate  on  standing. 
Starch  contains,  usually,  about  10-20  per  cent,  of  water,  which  may  be 
completely  driven  off  at  110°. 

Industrial  Uses. — The  industrial  applications  of  starch  are; 

i.  The  most  important  use  of  all  is  as  a  food  stuff.  As  starch 
occurs  naturally  in  most  plants,  it  is  the  most  abundant  of  all  carbohy- 
drate food  materials  for  animals  and  human  beings.  As  a  food,  starch 
is  used  mostly  in  its  naturally  occurring  form  in  the  plant,  such  as 


POLY-SACCHAROSES  365 

potatoes,  various  roots,  e.g.,  carrots,  beets,  parsnips,  etc.;  in  grains, 
e.g.,  wheat,  oats,  rice,  corn,  etc.;  and  in  greater  or  less  quantity,  in 
almost  all  plants  or  plant  parts  that  are  used  as  food. 

2.  A  source  of  alcohol  and  alcoholic  beverages.     The  starch  of 
grains,  potatoes,  etc.,  is  first  hydrolyzed  by  natural  sprouting,  as  in  the 
preparation  of  barley  malt,  or  by  the  addition  of  malt  to  it.     The 
hydrolytic  products,  glucose  and  maltose,  are  then  fermented  by  the 
addition  of  yeast,  containing  the  enzymes,  maltase,  and  zymase,  and 
alcohol  is  thus  produced.     This  has  been  fully  discussed  in  the  chapter 
on  alcoholic  fermentation,  (p.  95). 

3.  A  source  of  commercial  glucose.     Starch  from  various  sources, 
e.g.,  corn,  potatoes,  etc.,  is  hydrolyzed  by  boiling  with  dilute  sulphuric 
acid,  by  which  the  final  hydrolytic  product,  glucose,  is  obtained.     It  is 
ordinarily  obtained  as  a  thick  syrup,  corn  syrup,  or  as  a  crystalline 
substance,  glucose.     Corn  syrup  as  usually  made  is  not  pure  glucose 
syrup  but  contains  more  or  less  of  the  intermediate  products,  dextrin 
and  maltose.     With  these  present  the  syrup  does  not  crystallize  even 
when  very  concentrated. 

4.  As  a  coating  or  sizing  for  paper,  cloth,  etc.,  in  the  form  of  the 
mucilaginous  starch  paste.     Also  as  an  adhesive. 

Isolation  of  Starch. — Starch  is  also  used  as  a  food  in  its  pure  form. 
To  obtain  this  the  plant  part,  e.g.,  potatoes,  corn,  etc.,  is  macerated  and 
then  stirred  up  with  a  large  amount  of  water.  The  watery  mass  is 
passed  through  seives  to  remove  the  fibrous  material  while  the  starch,  in 
suspension,  passes  through.  On  allowing  the  starchy  liquid  to  settle 
the  starch  is  obtained  as  a  sediment  in  quite  pure  condition.  As  the 
materials  used  contain  relatively  little  else  than  starch  and  water 
there  is  not  much  foreign  substance  present.  Starch  so  prepared  is 
the  common  form  in  which  it  is  sold  under  the  names  of  corn  starch, 
and  laundry  starch,  the  former  used  as  a  food  and  the  latter  as  a  laundry 
sizing  material. 

The  three  most  common  substances  used  as  a  source  of  pure  starch 
contain  the  following  amounts. 

Plant  material  Calculated  on  Calculated  on 

fresh  substance,  dry  substance, 

per  cent.  per  cent. 

Potatoes,  (tubers)  18-21  72-84 

Wheat,      (grain)  56-65  66-72 

Corn,         (grain)  62-65  68-72 


366  ORGANIC  CHEMISTRY 

Cellulose 

Another  poly-saccharose  which  rivals  starch  in  its  wide  distribution 
in  nature  and  in  its  economic  importance  is  cellulose.  It  occurs  as  a 
universal  constitutent  of  the  cell  wall  of  plants.  In  young  cells  it  is 
probably  pure  but  in  older  cells,  especially  in  the  woody  tissue  of  large 
plants  such  as  trees,  it  has  become  hardened  by  the  infusion  of  gums 
and  resins.  Several  special  forms  of  cellulose  occur  as  the  fibres  of 
various  plants  such  as  cotton,  flax  (linen),  hemp,  sisal,  a  variety  of 
hemp,  jute  and  wood.  The  fibres  of  these  plants  have  great  industrial 
uses  and  give  to  cellulose  an  immense  economic  value.  Cotton  fibre 
is  practically  pure  cellulose.  The  name  cellulose  applies  not  to  a 
single  individual  compound  but  rather  to  a  group  of  compounds  of 
similar  character  and  occurrence.  While  it  is  practically  found  only 
in  plants  it  is  known  to  occur  in  some  animals.  Tunicin  is  an  example 
of  an  animal  cellulose  found  in  tunicates  and  is  considered  identical 
with  vegetable  cellulose. 

Normal  Cellulose. — Several  varieties  or  forms  of  cellulose  are  known 
as  found  in  plants.  Cotton  fibre  is  a  typical  and  practically  pure 
cellulose.  This  form  which  occurs  also  in  flax  and  hemp  is  termed 
normal  cellulose.  On  hydrolysis  it  yields  glucose  sugar  as  the  final 
product.  In  speaking  later  of  the  chemical  properties  of  cellulose 
it  is  the  normal  cellulose  which  is  considered.  Cotton  fibre  contains 
about  89-91  per  cent,  pure  cellulose,  8-10  per  cent,  water  and  only 
about  i  per  cent,  of  other  compounds  including  salts,  fats  and  proteins. 
Flax  and  hemp  stalks  yield  about  72  per  cent,  cellulose. 

Hemi-Cellulose. — Hemi-cellulose  is  the  name  applied  to  a  form  of 
compound  which  is  found  in  numerous  seeds  such  as  peas,  beans,  coffee, 
etc.,  and  which  differs  in  form  from  the  fibrous  variety.  It  is  probably 
simpler  or  perhaps  purer  than  normal  cellulose  and  hydrolyzes  more 
easily.  On  hydrolyzing  celluloses  of  this  type  yield  the  hexose  mono- 
saccharoses,  mannose  and  galactose  and  also  pentose  mono-saccharoses. 
They  are  therefore  included  in  the  group  of  poly-saccharoses  termed 
mannans,  galactans  and  pentosans  (p.  380) .  The  reserve  food  cellulose 
of  germinating  seeds  belongs  to  this  type. 

Compound  Celluloses. — Differing  from  both  of  the  preceding  varie- 
ties are  the  celluloses  which  are  present  in  the  cork  tissue  and  wood  of 
trees,  in  the  stalks  of  jute  and  ripe  grasses,  especially  the  cereals,  and  in 
the  parenchymatous  tissue  of  fruits.  The  celluloses  of  this  type  are 


POLY-SACCHAROSES  367 

termed  compound  celluloses  because  they  consist  of  two  parts,  viz.,  a 
cellulose  part  and  a  non-cellulose  part.  The  two  parts  are  probably 
in  real  combination.  The  compound  celluloses  are  of  three  classes. 

Ligno-Cellulose. — As  the  pure  cellulose  of  young  growing  cells 
becomes  older,  in  the  ripening  of  grasses  or  in  the  formation  of  the  woody 
tissue  of  trees,  the  cellulose  becomes  changed  by  the  infusion  of,  and 
probable  combination  with,  gums  and  resins  that  are  termed  in  general 
lignins.  These  lignins  are  probably  of  pentosan  character.  The 
resulting  compound  cellulose  is  termed  ligno-cellulose.  Wood  from 
spruce  trees  yields  about  50-55  per  cent,  .of  pure  lignin-free  cellulose 
while  hard  woods  like  oak  yield  only  about  35  per  cent.,  and  jute  stalks 
yield  about  54  per  cent. 

Pecto-Cellulose. — In  the  parenchymatous  tissue  of  grasses  and  of 
fruits  the  original  pure  cellulose  is  changed  to  a  compound  cellulose  by 
combination  with  gummy  compounds  known  in  general  as  pectins,  the 
compound  cellulose  being  termed  a  pecto-cellulose.  The  pectins  also 
are  probably  of  pentosan  character.  When  these  pecto-celluloses 
are  hydrolyzed  by  boiling  the  pectin  compounds  are  set  free  and  on 
cooling  gelatinize.  The  formation  of  fruit  jellies  is  the  result  of  such 
a  change. 

Adipo-Celluloses.— The  third  type  of  compound  cellulose  has  a 
non-cellulose  constituent  of  a  fatty  character  known  as  cutin.  The 
compound  cellulose  is  therefore  termed  an  adipo-cellulose,  or  a  cuto- 
cellulose.  Cellulose  of  this  variety  is  formed  in  the  cork  tissue  of 
plants  and  trees. 

In  all  of  these  occurrences  the  compound  celluloses  are  usually 
associated  with  more  or  less  normal  cellulose. 

Properties  of  Cellulose. — In  its  physical  character  cellulose  pos- 
sesses different  properties  such  as  fibrous,  cellular  or  woody  as  has  just 
been  discussed.  It  is  non-crystalline  and  probably  colloidal. 

Schweitzer's  Reagent. — Chemically  it  is  an  inert  compound  wholly 
insoluble  in  water,  most  neutral  reagents  and  in  dilute  acids  or  alkalies 
under  ordinary  conditions.  It  is  probable  that  no  solvent  dissolves 
cellulose  without  decomposition  or  hydration.  The  solvent  most 
commonly  used  is  an  ammoniacal  solution  of  copper  oxide  made  by 
dissolving  freshly  precipitated  copper  hydroxide  in  ammonium  hydrox- 
ide. This  solution  is  known  as  Schweitzer's  reagent.  After  solution 
in  this  reagent  acids  reprecipitate  the  cellulose  as  a  hydrated  cellulose. 


368  ORGANIC  CHEMISTRY 

Similarly  a  concentrated  solution  of  zinc  chloride  dissolves  cellulose 
as  a  hydrated  product. 

Xanth'c  Acid. — Another  solvent  of  cellulose  is  xanthic  acid,  also 
called  xanthonic  or  xanthogenic  acid.  Xanthic  acid  is  the  ethyl  ether 
of  -di-thio-carbonic  acid.  Its  formula  is  HS-CS-OC2H5.  When 
heated  with  water  to  500°  under  pressure  cellulose  is  dissolved  and 
undergoes  decomposition. 

Amyloid. — When  treated  with  concentrated  sulphuric  acid  cellulose 
dissolves  and  undergoes  hydrolysis.  If  the  solution  is  diluted  with 
water  a  gelatinous  product  is  obtained  which  gives  the  blue  color  with 
iodine  characteristic  of  starch.  This  product  is  known  as  amyloid. 
When  boiled  in  the  dilute  acid  the  amyloid  is  hydrolyzed  and  dextrin 
and  finally  glucose  are  obtained.  Concentrated  hydrofluoric  acid  and 
phosphoric  acid  also  dissolve  cellulose.  With  glacial  acetic  acid  in  the 
presence  of  acetic  anhydride  and  sulphuric  acid  cellulose  yields  acetyl 
derivatives  indicating  its  alcoholic  character.  From  the  products  of 
this  reaction  the  acetate  of  a  di-saccharose  is  obtained. 

Cellobiose. — This  di-saccharose  is  known  as  cellobiose.  With 
dilute  nitric  acid,  sp.  gr.  1.25,  cellulose  is  converted  into  oxy-cellulose. 

Nitro-Cellulose. — Concentrated  nitric  acid  together  with  sulphuric 
acid  however  yields  nitric  acid  esters  of  cellulose  known  as  nitro  cel- 
luloses which  have  important  industrial  uses  as  will  be  discussed  pres- 
ently. By  complete  oxidation  of  cellulose  with  nitric  acid  oxalic 
acid  is  obtained.  Dilute  solutions  of  alkalies  below  about  10  per  cent, 
have  no  action  on  cellulose.  When  however  cellulose  is  treated  with  a 
solution  of  sodium  hydroxide  above  10  per  cent.,  best  from  18  per  cent, 
to  28  per  cent,  sodium  cellulose  is  formed  and  this  with  water  yields  a 
hydrated  cellulose.  By  this  treatment  the  fibrous  character  of  cotton 
remains  but  the  fibres  possess  entirely  new  properties.  This  is  the 
basis  of  what  is  known  as  Mercerized  cotton  (p.  372).  On  prolonged 
treatment  with  strong  alkalies  or  by  fusion  cellulose  is  oxidized  to 
oxalic  acid 

Constitution. — A  study  of  the  hydrolytic  products  obtained  from 
cellulose  indicates  that  it  is  a  polysaccharose  carbohydrate  made  up  of 
hexose  mono-saccharose  units  and  in  the  hemi-celluloses  and  probably 
the  ligno-celluloses  the  units  may  also  be  pentose  mono-saccharoses. 
Normal  cellulose  is  probably  composed  of  glucose  units  only  while  the 
hemi-cellulose  may  contain  mannose  or  galactose  units.  In  regard  to 


POLY-SACCHAROSES  369 

the  size  of  the  molecule  all  the  evidence  indicates  that  it  is  larger  and 
probably  more  complex  than  starch  as  shown  by  the  formation  of 
amyloid.  That  it  is  not  simply  a  larger  molecule  than  starch  is  indi- 
cated by  the  fact  that  from  the  two  compounds  different  di-saccharoses 
are  obtained,  starch  yielding  maltose  whereas  cellulose  yields  cellobiose. 
In  any  poly-saccharose  made  up  of  a  large  number  of  hexose  units  by 
the  loss  of  water  from  each  two  units  linked  together  as  illustrated  in 
the  constitutional  formulas  for  the  di-saccharoses  (p.  354)  it  will  be 
seen  that  there  will  be  possible  only  three  hydroxyl  groups  in  each  C6  unit. 
This  is  important  in  connection  with  the  formation  of  nitric  acid  esters 
and  is  supported  by  the  fact  that  complete  nitration  of  cellulose  results 
in  the  tri-nitric  acid  ester  if  six  carbon  atoms  are  considered  as  the  unit. 
A  formula,  consisting  of  six  hexose  units,  has  been  suggested  by 
Hess. 

CH—O—CH—  CHOH—  CHOH—  CH—  CHOH—  CH2OH 


CH—O—CH^CHOH—  CHOH—  CH—  CHOH—  CH2OH 


CH—  O—  CH—  CHOH—  CHOH—  CH—  CHOH—  CH2OH 

I  -p^ 

XCH 

CH—  O—  CH—  CHOH—  CHOH—  CH—  CHOH—  CH2OH 

-O- 
CH—  O—  CH—  CHOH—  CHOH—  CH—  CHOH—  CH2OH 

-O— 

Cellulose—  (Hess) 
Industrial  Uses  of  Cellulose 

Cellulose  is  a  substance  of  immense  economic  value  because  of  the 
industrial  uses  made  of  it.  As  a  food  stuff  it  is  of  importance  only  in 
connection  with  herbiverous  animals.  The  products  made  from 
it  are  numerous  but  may  be  considered  under  two  heads.  I.  The 
utilization  of  the  fibrous  forms  of  cellulose,  more  or  less  purified 
but  unchanged  chemically,  for  the  manufacture  of  fabrics  or  other 
materials  in  which  the  fibre  is  the  important  thing.  This  includes 
all  kinds  of  cotton,  linen,  hemp  and  jute  goods  in  the  form  of 
thread,  string,  rope  or  cloth  and  also  paper  of  all  kinds.  II.  The 
transformation  of  cellulose  by  chemical  change  into  products  which 

24 


370  ORGANIC  CHEMISTRY 

may  retain  the  fibrous  character  but  which  in  most  cases  are  wholly 
different  from  the  original  material.  This  includes  the  manufacture 
of  such  products  as  Mercerized  cotton,  artificial  silk,  celluloid, 
collodion  and  cellulose  explosives  such  as  gun  cotton. 

Cotton  and  Linen  Cloth,  etc. — The  two  most  important  sources  of 
cellulose  for  the  manufacture  of  thread  and  cloth  and  similar  articles 
are  the  boll  of  the  cotton  plant  and  the  stalk  of  the  flax  plant.  The 
former  is  the  source  of  all  goods  known  as  cotton  while  the  materials 
made  from  the  latter  are  termed  linen.  Another  important  fibre  plant 
is  hemp,  the  leaves  or  stalk  of  which  yields  fibres  which  are  principally 
used  in  making  twine,  rope  and  canvas.  Several  varieties  of  hemp  are 
used  such  as  manila  hemp,  sisal,  etc.  The  stalk  of  the  jute  plant  is  the 
source  of  materials  out  of  which  sacking  or  burlap  and  carpets  are  made. . 
In  the  manufacture  of  these  products  the  fibre  of  the  plant  is  mechanic- 
ally separated  and  then  spun  into  thread  or  twisted  into  yarn  or  rope. 
The  thread  or  yarn  are  then  woven  into  fabrics.  The  products  possess 
properties  characteristic  of  the  particular  fibre  used.  As  in  the  manu- 
facture of  all  of  these  important  materials  the  cellulose  undergoes  no 
chemical  change  but  is  simply  mechanically  treated  no  further  details 
of  the  processes  will  be  given. 

Paper. — In  the  manufacture  of  paper  the  cellulose  also  undergoes 
no  chemical  change  other  than  purification  and,  in  the  case  of  ligno- 
cellulose  of  wood,  conversion  largely  into  normal  cellulose.  Pure  un- 
sized paper,  such  as  the  so-called  ashless  filter  papers  for  analyical  pur- 
poses, is  practically  pure  cellulose.  The  raw  materials  for  the  manu- 
facture of  paper  are  cotton  and  linen  rags,  wood,  straw  and  hemp.  The 
best  grades  of  writing  paper,  bond  papers,  were  originally  made  wholly 
from  linen  fiber  but  now  other  materials  are  used  together  with  linen. 
The  common  paper  such  as  that  used  for  newspapers  is  made  wholly  or 
largely  from  wood.  The  woods  used  are^r,  pine,  larch,  poplar,  birch  and 
beech. 

Wood  Pulp. — The  methods  for  converting  the  wood  into  pulp  are 
two,  viz.,  mechanical  and  chemical.  In  the  former  the  wood  is  mechani- 
cally cut  into  pieces,  the  knots  removed  and  then  the  pieces  shredded 
into  fibrous  material  and  carried  away  by  water.  By  the  action  of 
water  it  is  converted  into  a  pulp  and  separated  into  grades  by  means  of 
sieves.  The  fine  watery  pulp  is  then  pressed  into  sheets  and  dried. 
The  product  is  known  as  dry  pulp  and  is  stock  material  for  making 


POLY-SACCHAROSES  371 

over  into  finer  grades  of  paper.  In  the  chemical  process  the  wood  is 
similarly  cut  into  pieces  and  freed  from  knots.  The  small  chips  of 
wood  are  then  disintegrated  and  converted  into  pulp  by  the  chemical 
action  of  either  sodium  hydroxide  under  pressure  and  at  a  temperature 
of  170°  or  more  commonly  by  the  action  of  acid  sulphites  of  calcium 
or  magnesium,  Ca(HSOs)2  and  Mg(HSO3)2.  These  acid  sulphites 
are  made  by  the  action  of  sulphur  dioxide  and  water  upon  calcium  or 
magnesium  lime  stone.  The  acid  sulphite  liquor  is  introduced  into 
large  digesters  filled  with  the  wood  chips  and  heated  under  pressure 
to  130°.  After  digestion  the  soft  pulp  is  removed,  washed  with  water 
and  carried  away  by  water  through  a  series  of  sluice  ways  and  sieves. 
By  this  means  the  pulp  is  separated  into  grades  and  the  fine  pulp  car- 
ried finally  to  large  bleaching  vats  where  it  is  bleached  by  the  action 
of  chlorine  usually.  The  bleached  pulp  is  then  carried  by  water  over 
fine  wire  gauze  where  it  drains  of  much  water  and  then  it  is  passed  to 
heated  rolls  from  which  it  emerges  as  dry  sheet  pulp.  The  yield  of 
dry  pulp  by  either  process  is  bout  50-55  per  cent,  of  the  wood  used. 
An  electrical  process  has  also  been  used  in  which  sodium  chloride  is 
decomposed  by  the  electric  current,  the  wood  being  present  during  the 
electrolysis.  The  result  of  the  electrolysis  is  to  produce  chlorine, 
hypochlorous  acid  and  sodium  hydroxide,  all  of  which  effect  the  dis- 
integration of  the  wood. 

The  conversion  of  the  dry  pulp  or  other  paper  stock  into  finished 
paper  is  accomplished  in  general  as  follows.  Most  paper  is  a  mixed 
product  of  several  stock  materials  such  as  wood  pulp  and  pulp  from  cot- 
ton and  linen  rags.  The  dry  wood  pulp  together  with  varying  propor- 
tions of  cotton  rags  and  linen  rags  are  mixed  with  water  and  thoroughly 
disintegrated.  This  is  accomplished  in  large  drum-like  vats  with 
stirrers  and  sieves  known  as  Hollanders.  After  thorough  stirring  a  homo- 
geneous mixed  pulp  is  obtained  ready  for  the  rolls.  During  the  mixing 
further  bleaching  is  usually  effected  and  blueing  may  be  added  to  neu- 
tralize traces  of  yellow  color.  Also  inert  substances  such  as  barium 
sulphate  or  zinc  oxide  are  added  to  give  weight  and  rosin  is  used  for 
sizing.  The  pulp  is  then  drained  over  copper  gauze  and  passed  to  the 
rolls.  Before  passing  onto  the  rolls  the  paper  may  be  passed  through  a 
sizing  bath  to  give  a  smooth  gloss  surface.  From  the  rolls,  some  of 
which  are  heated,  the  paper  is  taken  off  as  finished  product.  The 
different  grades  and  qualities  of  paper  depend  upon  both  the  character 


372  ORGANIC  CHEMISTRY 

of  the  original  raw  material  used  and  upon  the  degree  of  purification 
to  which  it  has  been  subjected. 

Production  and  Consumption. — A  few  statistics  of  the  production 
and  consumption  of  paper  may  be  of  interest.  In  1906  the  world's 
production  of  paper  amounted  to  about  eight  million  tons.  In  1904 
the  United  States  produced  two  million  tons  of  pulp  and  four  million 
tons  of  paper.  The  amount  of  paper  used  annually  per  inhabitant  is 
about  as  follows: 

United  States  41.8  Ibs. 
England  37.4  Ibs. 

Germany          30.8  Ibs. 
France  25.3  Ibs. 

China  1.3  Ibs. 

Parchment  Paper. — We  have  previously  spoken  of  the  solvent 
action  of  concentrated  sulphuric  acid  on  cellulose.  If  instead  of  letting 
the  action  of  the  acid  continue  until  disintegration  of  the  cellulose 
occurs  it  is  stopped  soon  after  it  begins  and  the  acid  removed  by  thor- 
ough washing  with  water  the  paper  is  converted  into  a  hard,  tough  and 
semi-transparent  product  which  is  known  as  parchment  paper. 

Mercerized  Cotton. — Within  recent  years,  since  about  1896,  a 
form  of  cotton  known  as  Mercerized  cotton  has  become  a  definite 
article  of  commerce.  It  is  made  from  cotton,  usually  in  the  form  of 
thread  or  cloth,  by  chemical  treatment.  As  early  as  1844  Mercer, 
from  whom  the  material  is  named,  found  that  cold  sodium  hydroxide 
solution  of  about  20°— 30°  Baume,  (14-24  per  cent.)  converted  cotton 
cloth  into  a  stronger  more  silky  material  which  can  be  dyed  more 
easily  than  the  untreated  cotton.  The  chemical  and  physical  changes 
taking  place  have  been  shown  to  be  as  follows :  The  cold  alkali  converts 
the  cellulose  into  a  sodium  cellulose  compound,  and  this  on  washing  with 
water  is  converted  into  a  hydro-cellulose.  The  general  fibrous  form  re- 
mains unchanged  but  the  fibers  which  are  originally  flat  become  cyl- 
indrical and  thicker  or  more  compact  increasing  in  weight  by  8-10 
per  cent.  It  is  also  smooth  and  translucent  in  character  and  possesses 
a  luster  similar  to  that  of  silk.  On  drying  the  fiber  shrinks  to  75-80 
per  cent,  of  its  original  length  and  increases  in  strength  by  as  much  as 
68  per  cent.  If  the  process  is  carried  out  while  the  material  is  held  under 
tension  the  shrinking  is  prevented  while  the  thickening  and  change  in 


POLY-SACCHAROSES  373 

luster  take  place  as  originally  stated.  The  increase  in  strength  under 
tension  is  usually  about  35  per  cent.  The  silky  character  of  the  prod- 
uct may  be  increased  by  treatment  with  calcium  acetate,  soap  and 
acetic  acid  successively.  Not  only,  however,  does  Mercerized  cotton 
look  and  feel  like  silk  but  its  action  toward  dyes  is  also  like  that  of  silk 
and  it  can  be  colored  by  many  dyes  impossible  of  use  on  cotton.  On 
account  of  these  desirable  properties  it  has  become  an  important  article 
of  trade. 

Artificial  Silk. — While  Mercerized  cotton  has  the  general  appear- 
ance of  silk  it  is  not  what  is  known  as  artificial  silk  which,  while  also  a 
cellulose  product,  is  the  result  of  more  thorough  chemical  reaction. 
Artificial  silk  is  made  by  several  processes  and  the  different  varieties 
differ  slightly  though  the  chemical  nature  of  the  products  is  probably 
much  the  same.  The  raw  material  in  all  processes  is  cellulose,  usually 
in  the  form  of  cotton  waste  or  wood  fiber. 

I.  From  Mercerized   Cotton. — When   the   sodium  cellulose  pro- 
duced in  Mercerizing  cotton  is  dissolved  in  ammoniacal  copper  oxide 
(Schweitzer's  reagent)  and  the  solution  poured  into  sulphuric  acid  the 
cellulose  is  reprecipitated  as  an  oxidized  hydro-cellulose.     In  practice 
the  cotton  waste  after  purification  is  treated  with  sodium  hydroxide, 
copper  sulphate  and  ammonium  hydroxide  and  allowed  to  digest  until 
it  has  dissolved  to  a  stringy  mass.     This  is  then  filtered  under  pressure 
.and  the  cellulose  solution  is  forced  through  a  fine  set  of  capillary  tubes 
into  a  coagulating  solution.     This  coagulating  solution  may  be  sul- 
phuric acid  or  better  a  5  per  cent,  solution  of  sodium  hydroxide  which 
is  followed  by  a  dilute  sulphuric  acid  bath  to  remove  copper  hydrate. 
The  resulting  coagulated  cellulose  is  in  fine  filaments  which  are  spun 
into  thread  and  then  woven  into  other  desired  forms. 

II.  From  Nitro  Cellulose. — Historically  the  first  artificial  silk  was 
made  from  nitro  cellulose  by  Chardounet  in  1885.    Collodion  is  a 
mixture  of  the  lower  nitro  celluloses  or  nitric  acid  esters  of  cellulose 
made  by  nitrating  cellulose  incompletely.     It  had  been  found  that  fine 
fibers  of  collodion  could  be  used  in  preparing  the  carbon  filaments  for 
incandescent  electric  lights.     This  led  Chardounet  to  try  spinning  the 
filaments  of  collodion,  which  he  did  and  obtained  a  product  termed 
artificial  silk.     The  collodion  solution  in  alcohol-ether  is  forced  through 
fine  capillaries  as  in  the  preceding  process  and  as  the  solvent  rapidly 
evaporates,  fine  fibers  of  artificial  silk  are  obtained  which  may  be  con- 


374  ORGANIC  CHEMISTRY 

verted  into  thread  and  other  materials.  The  artificial  silk  so  made  is 
still  nitro  cellulose  and  while  not  explosive  it  is  very  inflammable.  To 
make  it  safe  to  use,  the  nitro  cellulose  is  denitrated  by  means  of  ferrous 
chloride,  formaldehyde  or  better  by  means  of  ammonium  hydrogen 
sulphide.  The  denitrated  product  is  probably  a  hydro-cellulose  of 
similar  character  to  that  obtained  from  Mercerized  cotton  and  it 
possesses  the  same  silk-like  character. 

Viscose  Silk.— III.  From  Cellulose  Xanthate.  We  have  referred 
to  the  solvent  action  of  xanthic  acid,  which  is  the  ethyl  ether  of  di- 
thio-carbonic  acid,  viz.,  HS-CS-OC2H5.  When  sodium  cellulose  is 
dissolved  in  xanthic  acid  the  cellulose  is  in  the  form  of  sodium  cellulose 
xanthate.  A  solution  properly  prepared  by  treating  cellulose  with 
sodium  hydroxide  and  carbon  di-sulphide  in  the  presence  of  benzene 
or  carbon  tetra-chloride,  in  which  polymerization  of  the  cellulose 
compound  is  effected,  is  decomposed  by  forcing  capillary  streams  of  the 
solution  into  a  solution  of  ammonium  sulphate.  The  cellulose  is 
thus  obtained  as  in  the  other  processes  in  the  form  of  fine  filaments  of  a 
hydrated  cellulose  possessing  silk-like  properties.  Artificial  silk  of 
this  type  is  known  as  viscose  silk  and  is  made  in  large  quantities.  In 
1914  about  20,000,000  pounds  of  artificial  silk  were  made,  of  which 
about  3,000,000  pounds  were  made  in  the  United  States.  Most  of  this 
product  was  viscose  silk. 

IV.  From  Cellulose  Acetate. — Solutions  of  cellulose  acetate  are 
prepared  by  treating  cellulose  with  a  mixture  of  acetic  and  phosphoric 
acids  and  dissolving  the  product  in  chloroform  or  better  in  formic  acid 
or  in  tetra-chlor  ethane.  The  solution  of  cellulose  acetate  is  treated 
and  converted  into  filaments  and  then  into  thread  and  other  materials 
by  similar  methods  to  those  already  given. 

In  all  of  the  varieties  of  artificial  silk  which  we  have  mentioned  the 
product  is  probably  in  the  form  of  hydrates  or  oxidized  hydrates  of 
cellulose.  This  cellulose  compound  is  obtained  as  fine  filaments  by 
spraying  the  solution  of  the  cellulose,  in  one  of  the  various  solvents, 
into  a  coagulating  solution.  The  filaments  are  then  spun  into  thread 
and  converted  into  other  forms  desired.  Whether  as  fiber,  thread, 
cloth  or  other  material  the  product  possesses  silk-like  properties  both 
as  to  luster,  feel  and  ability  to  react  with  dyes.  It  thus  has  many 
advantages  over  ordinary  cotton.  All  of  the  varieties  of  artificial 
silk  are,  however,  inferior  to  silk  itself  in  strength,  especially  when  wet, 


POLY-SACCHAROSES  375 

and  in  fineness  of  the  fiber.  In  luster  they  even  surpass  silk.  An 
illustration  of  the  difference  in  fineness  of  fiber  is  the  fact  that  the  fila- 
ments of  the  silk  cocoon  require  six  to  seven  million  meters  to  weigh 
one  kilogram  whereas  the  finest  fibers  of  viscose  silk  require  only  one 
million  meters  for  the  same  weight. 

Nitric  Acid  Esters. — As  cellulose  is  a  poly-hydroxy  alcohol  in  con- 
stitution it  forms  esters  with  scids.  The  acetate  and  nitrate  esters 
have  both  been  referred  to  in  connection  with  artificial  silk.  The  esters 
of  cellulose  and  nitric  acid,  usually  termed  nitro  celluloses,  have  other 
exceedingly  important  uses.  The  higher  nitrates  are  direct  explosives 
such  as  gun  cotton  and  the  lower  nitrates  are  the  basis  of  many  mixed 
explosives  and  smokeless  powders  and  also  of  the  very  important  sub- 
stance known  as  celluloid.  In  discussing  the  constitution  of  cellulose 
we  referred  to  the  probability  that  in  such  a  compound,  which  is  an 
anhydride  of  hexose  mono-saccharose  units,  there  will  remain  in  each 
unit  of  six  carbon  atoms  only  three  hydroxyl  groups  with  which  the 
compound  may  react  with  acids  forming  esters.  This  is  borne  out  by 
the  fact  that  the  highest  nitric  acid  ester  obtained  contains  only  three 
nitric  acid  groups  per  unit  of  six  carbon  atoms.  It  is  claimed  that 
higher  esters  have  been  prepared  but  it  is  probable  that  in  them  more 
than  six  carbon  atoms  are  considered  in  proportion  to  the  nitric  acid 
groups.  The  exact  constitution  or  even  composition  of  the  cellulose 
nitrates  used  in  the  important  products  mentioned  is  unknown  due  to 
the  character  of  the  reaction  of  nitration.  The  reaction  is  progressive 
and  more  and  more  nitric  acid  enters  the  cellulose  molecule  as  the  re- 
action continues  by  indefinite  stages.  The  result  is  a  series  of  nitrates 
which  are  mixed  in  some  instances  with  hydro-celluloses,  oxy-celluloses 
and  nitrates  formed  from  them  and  also  with  other  esters  formed  with 
the  sulphuric  acid  always  present  during  nitration.  It  is  thus  not  sur- 
prising that  no  nitrate  of  cellulose  or  derivative  of  it  has  ever  been 
prepared  as  a  distinct  individual.  Neither  has  one  ever  been  crystal- 
lized, distilled  or  vaporized  unchanged.  We  thus  see  that  statements 
in  regard  to  the  composition  of  the  various  products  made  from  these 
esters  must  be  more  or  less  general  and  indefinite.  Furthermore,  the 
nomenclature  of  the  products  is  somewhat  confused  due  to  the  variety 
of  uses  to  which  they  are  put. 

Pyroxylin. — The  term  pyroxylin  is  generally  used  in  this  country  as 
applying  to  the  lower  cellulose  nitrates  containing  about  10.5-12.2 


376  ORGANIC  CHEMISTRY 

per  cent,  nitrogen,  which  are  soluble  in  amyl  acetate  and  in  methyl 
alcohol  and  are  used  in  preparing  lacquers  and  in  making  artificial  silk 
and  celluloid. 

Collodion. — Collodion  and  photo-cotton  are  terms  often  used  prac- 
tically synonymously  with  pyroxylin  but  apply  more  specifically  to 
lower  nitrates,  soluble  in  alcohol-ether.  Collodion  is  used  in  pharmacy 
and  as  a  coating  for  sensitive  photographic  plates. 

Pyro-Collodion. — The  terms  pyro-collodion  and  collodion  cotton 
are  used  to  designate  Ipwer  nitrates  of  cellulose  containing  about  12.6 
per  cent,  nitrogen,  more  or  less  soluble  in  alcohol-ether  and  used  in  the 
manufacture  of  smokeless  powders. 

Gun  Cotton. — Finally  the  highest  nitrates  of  cellulose,  containing 
about  13.4  per  cent,  nitrogen  and  probably  the  tri-nitrate,  constitute  the 
explosive  known  as  gun-cotton,  explosive  cotton  or  ballistic  cotton. 
They  are  practically  insoluble  in  alcohol-ether. 

Celluloid. — One  of  the  most  interesting  products  made  from  the 
cellulose  nitrates  is  celluloid.  When  pyroxylin  is  mixed  in  definite 
proportions  with  camphor  in  the  presence  of  alcohol  a  dough-like  mass 
is  obtained  which  when  subjected  to  heat  and  pressure  forms  a  homo- 
geneous product  that  when  cold  is  hard  and  brittle  but  when  hot  is 
plastic.  It  is  thus  able  to  be  molded  into  various  shapes  or  it  may  be 
cut  or  sawed  and  polished.  In  thin  sheets  it  is  transparent  but  is  opaque 
in  thick  pieces.  It  may  be  made  more  opaque  by  the  addition  of  zinc 
oxide  or  similar  inert  substances  and  it  may  be  dyed  or  colored  with 
pigments.  By  various  treatments  celluloid  is  thus  possible  of  use  in  a 
great  variety  of  ways  and  many  toilet  articles,  novelties  and  other 
products  are  common  forms  in  which  it  is  known.  From  it  very  good 
imitations  of  ivory,  tortoise  shell,  onyx,  window  glass,  etc.,  are  made 
and  widely  used.  Its  disadvantage  is  its  inflammability  which,  though 
diminished  by  addition  of  mineral  substances,  has  never  been  wholly 
prevented. 

Cellulose  Explosives. — The  explosives  made  from  cellulose  are  of 
two  kinds,  viz.,  cellulose  nitrates  alone,  as  in  gun  cotton,  and  mixtures 
of  cellulose  nitrates  and  nitro-glycerol  which  constitute  the  smokeless 
powders  made  from  cellulose  nitrates. 

Gun  Cotton. — As  nitric  acid  esters  of  poly-hydroxy  alcohols,  the 
two  important  explosives  nitro  glycerol  and  gun  cotton  are  exactly 
analogous  not  only  in  character  but  also  in  the  fact  that  each  is  the 


POLY-SACCHAROSES  377 

fully  nitrated  product  of  the  alcohol  compound  from  which  it  is  made. 
Considered  as  the  cellulose  tri-nitrate  gun  cotton  has  the  empirical 
formula  C6H7O2  (ONO2)3. 

Nitration. — In  the  nitration  process  for  the  manufacture  of  the 
various  cellulose  nitrate  products,  whether  as  pyroxylin,  pyro -collodion 
or  gun  cotton,  cellulose  in  the  form  of  purified  and  dried  cotton,  usually 
cotton  waste,  though  in  some  cases,  as  in  making  pyroxylin  for  celluloid, 
tissue  paper  is  used,  is  treated  with  a  mixture  of  nitric  and  sulphuric 
acids.  The  proportions  and  concentrations  of  the  acids  and  the  length 
of  time  and  temperature  of  the  nitration,  while  definite  for  each  prod- 
uct, vary  considerably  according  to  the  degree  of  nitration  desired. 
In  the  ordinary  process  known  as  dipping,  the  cotton  is  immersed  in 
the  acid  bath  for  about  ten  minutes,  then  removed  from  the  bath  and, 
while  wet  with  the  acid,  placed  in  earthen  pots  which  are  kept  cold. 
The  digestion  in  these  pots  continues  for  about  twelve  hours,  in  the 
case  of  gun  cotton,  after  which  the  cotton  is  placed  in  a  centrifuge  and 
the  greater  part  of  the  acid  removed.  In  another  process  the  nitration 
is  carried  on  in  the  centrifuge.  In  the  Thomson  displacement  process 
the  cotton  is  placed  in  the  acid  bath  and  allowed  to  remain  for  about 
two  hours.  Cold  water  is  then  allowed  to  flow  in  slowly  at  the  top 
while  the  acid  is  withdrawn  at  the  bottom.  After  about  three  hours 
the  water  replaces  the  acid  almost  completely  and  without  heat. 
As  either  gun  cotton  or  any  of  the  other  products  must  be  definite  in 
respect  to  nitrogen  content  frequent  control  analyses  are  necessary  at 
the  first,  until  the  conditions  of  nitration  are  fixed.  After  the  nitrated 
cotton  is  centrifuged  it  is  thoroughly  washed  and  boiled.  Before  boiling 
the  gun  cotton  is  fibrous,  of  the  same  general  character  as  the  original 
cotton.  The  boiling  not  only  removes  the  last  traces  of  acid  but  the 
fibrous  material  is  converted  into  a  pulp  or  colloidal  product  which  is 
more  stable.  After  boiling  the  gun  cotton  is  drained  of  most  of  the 
water  leaving  a  product  containing  about  25  per  cent,  water.  For  use 
in  mine  cartridges  and  torpedoes  the  moist  gun  cotton  is  compressed, 
by  which  treatment  it  is  made  safer  and  more  powerful  in  its  explosive 
force.  Gun  cotton  is  soluble  in  benzene,  ethyl  acetate,  acetone  and 
nitro  benzene  but  is  insoluble  in  water,  alcohol,  ether,  acetic  acid  or  in 
nitro  glycerol.  It  is  an  extremely  strong,  shattering,  non-propelling 
explosive  and  when  moist  or  compressed  is  usually  exploded  by  means 
of  a  detonator  of  dry  gun  cotton  which  is  ignited  by  a  fulminating  cap. 


ORGANIC  CHEMISTRY 

When  unconfined  and  ignited  it  burns  rapidly  but  without  explosion. 
The  decomposition  products  of  either  burning  or  explosion  are  carbon 
mon-oxide,  CO,  carbon  di-oxide,  CO2,  water,  H2O,  hydrogen,  H2, 
and  Nitrogen,  N2.  It  is  therefore  smokeless 

2C6H702(ON02)3  -  ->  5CO+7C02+3H20+4H2+3N2 

i  kilogram  of  gun  cotton  yields  741  liters  of  gas  at  ordinary  temperatures 
or  982  liters  if  the  temperature  is  above  the  boiling  point  of  water.  The 
chief  uses  of  gun  cotton  as  such  are  in  torpedoes,  grenades  and  mine 
cartridges,  though  for  military  purposes  it  is  now  largely  replaced  by 
other  high  explosives  such  as  tri-nitro  toluene,  T.N.T.,  and  tetryl 
(see  Part  II). 

Cordite,  Smokeless  Powders,  etc. — While  gun  cotton  is  insoluble  in 
nitro  glycerol,  when  the  two  are  mixed  and  treated  with  acetone  and  a 
little  vaseline,  a  gelatinous  paste  is  obtained  which  is  known  as  cordite. 
This  is  one  of  the  smokeless  powders  made  from  nitro  celluloses  and 
possesses  propelling  properties  unlike  gun  cotton.  The  first  smokeless 
powder  was  made  by  Vieille,  in  1884,  who  destroyed  the  shattering 
non-propelling  action  of  gun  cotton  by  converting  it  from  a  fibrous  to  a 
non-fibrous  substance,  by  dissolving  the  gun  cotton  and  then  allowing 
the  solvent  to  evaporate.  Most  of  the  smokeless  powders  containing 
nitro  celluloses  are,  however,  made  from  the  lower  nitrates,  pyro-col- 
lodion,  and  not  from  gun  cotton.  Collodion  cotton  when  mixed  to  the 
amount  of  2-10  per  cent,  with  nitro  glycerol  forms  gelatinous  products 
which  have  lost  more  or  less  of  the  shattering  properties  of  gun  cotton 
and  have  taken  on  propelling  properties  necessary  for  gun  cartridges 
and  shells.  The  varieties  of  the  products  obtained  are  many  depending 
upon  the  proportion  of  collodion  and  the  amount  of  nitrogen  in  the 
collodion.  Some  are  used  for  blasting  purposes  while  others  are  used 
in  guns.  They  are  termed  in  general  gelatin  powders,  blasting  gela- 
tins or  gum  dynamites,  the  latter  containing  some  absorbent  sub- 
stance like  wood  meal  or  sodium  nitrate.  The  first  explosives  of  mixed 
nitro  glycerol  and  nitro  celluloses  were  made  by  Nobel  already  referred 
to  in  connection  with  dynamite  (p.  202).  One  of  these  is  known  as 
ballistite  and  consists  of  about  50  per  cent,  nitro  glycerol  and  50  per  cent, 
of  collodion  cotton  containing  11.2-11.7  per  cent,  nitrogen.  All  of  these 
smokeless  po.wders  and  gum  dynamites  possess  advantages  over  either 
nitro  glycerol  or  gun  cotton  and  are  much  used  in  both  military  opera- 
tions and  blasting.  In  the  former  use,  however,  they  have  been  more  or 


POLY-SACCHAROSES 


379 


less  replaced  by  modern  high  explosives  before  referred  to.  Up  to 
certain  limits  the  higher  the  proportion  of  collodion  cotton  to  that  of 
nitro  glycerol  the  greater  is  the  propelling  force  and  the  less  the  shattering 
action.  For  the  purpose  of  comparison  at  this  time  the  relative  ex- 
plosive force  of  some  explosives  is  given. 

EXPLOSIVE  FORCE  OF  EXPLOSIVES 


Explosive 

Wt.  of  explosive, 
kilograms 

Energy  in 
kilogram  -m  eters 

Nitro  glycerol  

O 

680,000 

Explosive  gelatine 

o 

6co,ooo 

Dynamite 

O 

<oo  ooo 

Gun  cotton  

O 

4^6,000 

Potassium  picrate 

o 

•230  ooo 

Mercury  fulminate  

.O 

170,000 

Nitrogen  chloride 

o 

144  OOO 

The  preceding  discussion  of  the  industrial  products  obtained  from 
cellulose  while  not  complete  nor  in  technical  detail  emphasizes  the 
striking  fact  that  cellulose,  a  widely  distributed  natural  substance, 
complex  in  its  constitution  and  inactive  in  its  properties,  may,  by  either 
mechanical  treatment  or  chemical  reaction,  be  converted  into  such 
important  products  as  thread,  string  and  rope;  wearing  apparel 
(cotton  and  linen),  Mercerized  cotton,  artificial  silk;  collodion,  cellu- 
loid, smokeless  powders  and  high  explosives. 
Dextrin,  Glycogen,  Inulin 

Dextrin. — The  three  poly-saccharoses,  dextrin,  glycogen  and  inulin 
are  all  compounds  possessing  the  same  empirical  formula  as  starch, 
viz.,  (C6HioC5)x.  Dextrin  results  from  the  diastase  hydrolysis  of 
starch  and  on  that  account  is  believed  to  have  a  constitution  that  is 
less  complex  than  that  of  starch.  It  is  found  together  with  starch  and 
sugar  in  plants  and  in  vegetable  juices.  It  is  prepared  by  hydrolyzing 
starch  with  either  diastase  or  acids.  Several  forms  or  varieties  are 
known,  or  have  been  found  by  distinct  tests  to  result,  as  intermediate 
products,  in  the  hydrolysis  of  starch  to  maltose  (p.  364).  It  is  soluble 
in  water,  reduces  Fehling's  solution,  and  reacts  with  phenyl  hydrazine. 
In  regard  to  these  two  reactions,  however,  there  is  some  question  as  it 
is  doubtful  if  the  reactions  have  been  obtained  with  absolutely  pure 
substance.  One  of  the  varieties  of  dextrin  gives  a  red  color  with  an 
iodine  solution.  On  this  account  it  is  known  as  erythro-dextrin.  Other 


380  ORGANIC  CHEMISTRY 

varieties  give  no  color  with  iodine  and  are  known  as  achroo-dextrins. 
Dextrin  is  not  fermented  by  zymase  but  is  hydrolyzed  by  diastase  yielding 
maltose.  By  the  complete  hydrolysis,  by  means  of  acids,  dextrin 
yields  glucose.  The  natural  plant  gums  are  probably  related  to  dex- 
trin in  regard  to  the  complexity  of  the  molecule.  The  gums  yield, 
mostly,  pentose  sugars  on  hydrolysis,  i.e.,  they  are  pentosans,  whereas 
dextrin  yields  glucose  and  may  be  termed  a  hexosan. 

Glycogen. — As  previously  stated  starch  does  not  occur  in  animals. 
Glycogen,  however, which  is  isomeric  with  starch,  does  occur  in  animals 
and  on  this  account  it  is  known  as  animal  starch.  It  is  found  in  the 
liver  and  muscles  of  animals  where  it  is  present  as  a  reserve  food  material 
analogous  to  starch  in  plants.  It  is  built  up  (anabolized)  in  the  animal 
from  the  hexose  mono-saccharose  products  of  the  digestion  of  carbo- 
hydrate food.  It  is  present  in  the  liver  to  as  much  as  10  per  cent  of 
its  weight  and  in  muscular  tissue  to  about  2  per  cent.  When  it  is 
used  by  the  animal  as  food  it  is  again  split  into  glucose,  probably  by  an 
enzyme  termed  glycogenase.  The  glucose  then  enters  the  blood 
circulation  and  is  carried  to  the  cells  where  it  is  oxidized  with  the  pro- 
duction of  energy.  Glycogen  is  a  white  amorphous  powder  soluble  in 
water.  It  is  dextro  rotatory  and  is  colored  brown  with  iodine.  By 
acid  hydrolysis  it  yields  dextrin,  then  maltose  and  finally  glucose. 

Inulin. — Inulin  is  found  in  certain  plants,  especially  in  the  tubers 
of  the  Dahlia.  It  is  isomeric  with  the  other  poly-saccharoses  and  is 
also  a  reserve  food  material.  It  is  a  white  powder  soluble  in  water. 
It  is  lew  rotatory  and  gives  no  color  with  iodine.  '  It  is  not  hydrolyzed 
by  diastase  but  by  a  particular  enzyme  known  as  inulase.  Its  peculiar 
characteristic  is  that  by  acid  hydrolysis  it  yields  only  fructose. 

Mannans  and  Galactans 

Two  other  hexosan  poly-saccharoses  resembling  starch  and  cellulose 
should  be  mentioned.  Mannans  are  poly  saccharoses  which  on  hydro- 
lysis yield  mannose.  They  are  present  in  vegetable  ivory.  Galactans 
are  similar  poly  saccharoses  which  yield  galactose  on  hydrolysis.  The 
substance  known  as  agar-agar  is  a  galactan.  Both  of  these  poly-sac- 
charoses are  associated  in  small  amounts  with  cellulose  in  many  plants, 
e.g.,  in  wheat  and  other  cereals,  and  in  numerous  seeds,  especially 
legumes. 

The  following  tabular  summary  of  the  carbohydrates  may  be  of 
value. 


CARBOHYDRATES 


H 

CJ             UJ                     <D     03                                                    4> 

iiiiiiii     sislss'sls    1    8  §  1 

,52,313,3.3213.3      .3      .3  .3  2 
O  EH  O  O  O  O  Pn  O  O       O       OOfe 

HI 

iiiiiiii      8  •§  8  I  8  <--        S     1  !  11  « 

.3  2  .2  "3  -S             "3      *  13  *  "3  2 
OfeOOO               S       SooSfo 

ill 

<L> 
1£                                                                                  M      * 

11111111       8  2  8      3  -          1  -ll  1  1  1  1 

2^5      -2              -Sl33o8l»^ 

Ifij    s        S|t*|*l 

Alcoholic 
fermenta- 
tion by 
zymase 

+iiii+++i       i       ii          i       i       iii 

ill 

++++++++      i      +     +i          i       i       ill 

ill 
III 

fr.    M    IH 

+  +  +  +  +  +  +  +       1       +      -HI            1        1        III 

tP 

£  £  Q  Q  Q  Q  j  Q       Q       Q       Q  Q 

2'g  00  O     • 

wlg^Q 

.^•SS  333 

^^^^^oSoaoy     Q     Q     Q- 
Q  Q  B  Q  Q  Q  Q                     :          -               :  :  • 

Structural 
formula, 
aldehyde 
or  ketone 

k^         <U                                        .         *                         :                                                      •         • 

^<<<<<t4<     I     *     <  :                        :  : 

Composition 
formula 

s     s     s  s       ^    ^    '5'5'S 

^^qocScDoq     9     9     99        9     9     999 

ffiffiWWWWWW      *      *      ^^          *S      €      ^^^ 

o  o  o  o  o  o  o  o     o     o     oo         ^.     c.     c,c.cs- 

1 

:::::::                          '          '.                '.   '. 

.......                          . 

ii|jis:i!  ai  s  if       i  ig!j 
•^^^sj'2^!  §  ^  3^    ^'  ^  OQ^ 

382  ORGANIC  CHEMISTRY 

XI.  AMINO  ACIDS  AND  PROTEINS 
A.  AMINO  ACIDS 

The  amino  acids  like  the  hydroxy  acids  and  the  halogen  acids  belong 
to  the  class  of  substituted  acids.  In  them  an  amino  group  ( — NH2) 
is  substituted  in  the  non-carboxyl  part  of  the  acid.  They  were  not 
discussed  with  the  other  substituted  acids  because  we  wished  to  con- 
sider at  one  time  both  the  amino  acids  derived  from  mono-basic  acids 
and  those  derived  from  di-basic  acids  in  connection  with  the  proteins 
which  we  shall  find  are  related  compounds. 

Synthesis  from  Halogen  Acids. — The  simplest  method  for  the  syn- 
thesis of  amino  acids  is  by  the  action  of  ammonia  on  the  halogen  acids 
and  is  exactly  analogous  to  the  formation  of  alkyl  amines  from  alkyl 
halides. 

CH2(C1)— COOH  +  H)— NH2       ->     CH2(NH2)— COOH  -f   HC1 

Chlor  acetic  acid  Ammo  acetic  acid 

From  Aldehydes. — Aldehydes  and  ketones  by  the  hydrogen  cyanide 
reaction  yield  cyan-hydrine  compounds  which  are  nitrites  of  hydroxy 
acids.  When  such  an  hydroxy  acid  nitrile  is  treated  with  ammonia 
the  hydroxyl  group  is  replaced  by  the  amino  group  forming  the  nitrile 
of  the  amino  acid,  the  amino  acid  itself  being  obtained  on  hydrolysis 
of  the  nitrile. 

H  H 

I  I 

CH3— C  =  O  +  H— CN    >    CH3— C— CN  +  NH3     — + 

Acetaldehyde 


Nitrile  of  a-hydroxy 
propionic  acid 


OH 

Of  tt-t 

donic  i 

H  H 

CH3— C— CN  +  H2O    >      CH3— C— COOH 


NH2  NH2 

Nitrile  of  a-amino  o-Amino 

propionic  acid  propionic  acid 


AMINO   ACIDS  383 

CH,  CH3 


CH3— C  =  O  +  H— CN       -*    CH3— C— CN  +  NH3 

Acetone  I 


Nitrile  of  a-hydroxy 
iso-butyric  acid 


OH 

f  a-hj 
ityric  i 

CH3  CH3 

I  I 

CH3— C— CN  +  H2O    >      CH3— C— COOH 

NH2  NH2 

Nitrile  of  a-amino  a-Amino  iso- 

iso-butyric  acid  butyric  acid 

By  this  synthesis,  it  will  be  noticed  that  the  alpha-a,mmo  acids  result 
as  the  amino  group  is  always  linked  to  the  carbon  to  which  the  carboxyl 
is  also  linked.  The  amino  acid  will  also  contain  one  more  carbon  than 
the  aldehyde  or  ketone  due  to  the  addition  of  the  cyanide  radical, 
i.e.,  acetic  aldehyde  yields  amino  propionic  acid  and  propanone  (ace- 
tone) yields  amino  iso-butyric  acid. 

From  Oximes  and  Hydrazones. — The  oximes  and  hydrazones  ob- 
tained from  ketone  acids  yield  amino  acids  on  reduction  with  sodium 
amalgam  and  glacial  acetic  acid. 
CH3— C— CH2— COOR 

+  H2)  =  NOH  --> 

(f\\  Hydroxyl 

\w/  amine 

Aceto-acetic  acid 

(ester) 

CH3— C— CH2— COOR       (+H)     CH3— CH— CH2— COOR 
N— OH  NH2 

Oxime  of  aceto-acetic  acid  /3-Amino  butyric  acid 

(ester)  (ester) 

CH3— C— CH2— COOR 

+  H2)  =  N— HN— C6H5 > 

/r\\  Phenyl  hydrazine 

Aceto-acetic  acid 

(ester) 

CH3— C— CH2— COOR     (+H)    CH3— CH— CH2— COOR 
N— HN— C6H5  NH2 

Phenyl  hydrazone  /3-Amino  butyric  acid 

of  aceto-acetic  acid  (ester) 

(ester) 


384  ORGANIC  CHEMISTRY 

By  this  synthesis  the  alpha-ketone  acids  yield  alpha-amino  acids  and 
the  beta-ketone  acids  yield  foto-amino  acids,  etc.,  and  there  is  no  in- 
crease in  the  number  of  carbons  in  the  chain. 

From  Proteins. — The  most  important  method  of  preparing  amino 
acids  is  not  a  true  synthesis  but  a  splitting  of  complex  compounds. 
This  is  the  hydrolysis  of  proteins  which  will  be  discussed  a  little  later. 
The  amino  acids  are  of  especial  importance  because  they  are  di- 
rectly connected  with  the  living  processes  of  plants  and  animals  through 
the  protein  constituents.  They  are  formed  from  the  proteins  by  en- 
zymatic or  bacterial  fermentation  or  by  acid  hydrolysis.  They  are 
crystalline  compounds  readily  soluble  in  water,  usually  possessing  a 
sweet  taste.  In  their  general  character  they  resemble  the  hydroxy 
acids  reacting  readily  and  thus  lending  themselves  to  investigation. 

Acid  and  Basic. — As  the  amino  acids  contain  both  an  amino  group 
and  a  carboxyl  group  they  react  both  as  acids  and  as  bases.  In  this 
double  role  they  exhibit  very  interesting  properties.  This  same  double 
character  of  acid  and  base  has  also  been  ref erred^  to  in  connection  with 
the  hydroxy  acids.  In  this  case  the  basic  character  is  due  to  the  pres- 
ence of  an  alcoholic  hydroxyl  group  and  is  consequently  weak.  With 
the  amino  acids,  however,  the  basic  character  is  due- to  the  presence  of 
the  much  more  basic  amino  group  so  that  the  double  acid  and  basic 
character  of  the  compounds  is  more  pronounced.  As  acids  the  amino 
acids  yield  esters  and  acid  chlorides. 

CH2(NH2)— COOR        CH2(NH2)— COC1 

Ester  of  amino  acetic  acid  Amino  acetic  acid  chloride 

Esters. — The  esters  are  of  interest  because  it  has  been  through  them 
that  the  separation  of  amino  acids  obtained  by  the  hydrolysis  of  proteins 
has  been  accomplished. 

Primary  Amines. — As  primary  amines  the  amino  acids  react  with 
nitrous  acid  in  the  distinctive  way  (p.  60)  and  the  amino  group  is 
replaced  by  the  hydroxyl  group  yielding  the  corresponding  hydroxy  acid. 

HO— |N=  (O  +  H2)  =  N|— CH2—  COOH    > 

Nitrous  acid  Amino  acetic  acid 

HO— CH2— COOH  +  N2  +  H20 

Hydroxy  acetic  acid 

Salts. — The  most  interesting  and  important  derivatives  of  the 
amino  acids  are  the  salts.  Reacting  as  an  alkyl  amine  they  yield  salts 
with  acids  and  as  an  acid  they  form  salts  with  bases. 


AMINO    ACIDS  385 

C1H—  H2N—  CH2—  COOH  «-  -  HC1  +  H2N—  CH2—  COOH  + 

Amino  acetic     <  ---     reacting         <  ---    Amino  acetic  acid    -  —  > 
acid  hydro-  as  a  base 

chloride 

KOH       —  »    H2N—  CH2—  COOK 

reacting  as        --  >    Potassium  amino 
an  acid  acetate 

Inner  Salts.  —  We  would  also  expect  inner  salts  to  be  formed  in  which 
the  basic  amino  group  neutralizes  the  acid  carboxyl  group  in  the  same 
molecule. 


2, 
COOH  XCOO 

Amino  acetic  acid  Inner  ammonium  salt 

The  existence  of  such  an  inner  salt  is  well  established  by  the  physical 
properties  of  many  amino  acids  and  by  the  chemical  reactions  of  the 
higher  alkylated  amino  derivatives  formed  by  converting  the  primary 
amine  group  into  secondary  and  tertiary  alkyl  amine  groups. 

CH2(C1)—  COOH+H)NH2  -  >  CH2(NH2)—  COOH  (primary  amine) 

Chlor  acetic  acid  Ammonia  Amino  acetic  acid 

CH2(C1)—  COOH  +  H)NHCH3    -  >    CH2(NHCH3)—  COOH 

Methyl  amine  *«*£?*  (secondary  amine) 


CH2C1)—  COOH  +  H)N(CH3)2    -  >     CH2(N(CH3)2)—  COOH 

Di-methyl  amine  Di-methyl  amino    /  ,      .  •  •      \ 

acetic  acid       (tertwy  amine) 

The  tertiary  amine  group  in  this  last  compound  being  more  strongly 
basic  than  the  primary  amine  group  in  amino  acetic  acid  would  more 
readily  form  an  inner  ammonium  salt.  There  is  also  a  tetra-methyl 
ammonium  iodide  compound  formed  analogous  to  the  tetra-methyl 
ammonium  salts  of  the  alkyl  amines. 

XN(CH3)2  XN(CH3)3I 

CH/  +  CH3—  I       ~>    CH/ 

XCOOK  XCOOK 

Di-methyl  amino  Tetra-methyl  ammonium  iodide 

acetic  acid  (salt)  (salt) 

With  acids  this  salt  loses  potassium  iodide,  KI,  and  yields  an  acid. 
This  acid  has  the  constitution  of  an  inner  salt  and  would  be  related 
to  what  we  may  term  the  normal  tetra-methyl  ammonium  iodide 
acid,  by  the  loss  of  hydrogen  iodide,  and  to  a  tetra-methyl  ammonium 

25 


386 


ORGANIC  CHEMISTRY 


hydroxide   compound,    by   the  loss  of  water,  i.e.,  as  an  anhydride. 
These  relationships  may  be  represented  as  follows 


CH2. 

XCOOH 

Tetra-methyl 

ammonium  acetic 

acid  iodide 

(normal  acid) 


(-KI) 


CH2v 

XCOO(K 

Potassium  tetra- 

methyl  ammonium 

acetic  acid  iodide 

(salt) 


CH 


CO 

Tetra-methyl 
ammonium  acetic  acid 

(inner  salt) 


-HOH 


N=(CH3)3 
/\(OH) 

2v 

XCOO(H) 

Tetra-methyl 
ammonium  acetic  acid 
hydroxide 

(acid) 

Anhydrides,  Di-keto-piperizines.  —  By  far  the  most  important 
derivatives  of  amino  acids  are  the  anhydrides  and  a  related  group 
known  as  poly-peptides.  When  the  ester  of  an  amino  acid  is  prepared 
it  readily  loses  two  molecules  of  alcohol  and  yields  a  double  anhydride. 
Such  an  anhydride  is  not  an  inner  compound  like  the  one  above  as 
water  or  alcohol  is  lost  by  the  interaction  of  two  molecules  of  the  acid 
or  the  ester  as  follows. 


CH2— CO(OR 

I  +  I 

NH(H        RO)OC— CH 

Amino  acetic  acid  ester 

(2  mol.) 


H)NH     (— 2R— OH)     CH2 CO NH 


NH- 


CH2 

Amino  acetic  acid  anhydride 


These  anhydrides  are  known  as  di-keto  piperazines. 

Polypeptides. — When  these  anhydrides  are  treated  with  dilute 
alkali,  Emil  Fischer  found  that  one  molecule  of  water  is  restored,  the 
compound  resulting  being  as  follows: 


H)HN— CH2— CO— NH— CH2— CO(OH 

Poly-peptide 


CH2— CO— NH 
|  |    +  H20  - 

NH— OC— CH2 

Amino  acetic  acid  anhydride 

These  new  compounds  Fischer  called  peptides  or  poly-peptides,  as  they 
are  made  up  of  two  or  more  molecules  of  an  amino  acid.  This  poly- 
peptide  or  di-peptide  of  amino  acetic  acid,  which  would  be  called 


AMINO   ACIDS  387 

amino  aceto  amino  acetic  acid,  is  better  termed  glycyl  glycine,  glycine 

being  another  name  for  amino  acetic  acid.  These  poly-peptides  form 
the  connecting  link  between  simple  compounds  like  amino  acetic  acid 
and  the  very  complex  proteins.  We  shall  discuss  this  presently. 
Plainly  a  di-peptide,  where  it  has  two  residues  of  the  same  amino 
acid,  is  intermediate  between  the  amino  acid  and  the  amino  acid 
anhydride,  being  the  single  anhydride  of  the  amino  acid. 

CH2— CO(OH        H)HN  (-H— OH)        CH2 CO NH 

I  +  I  I  I 

NH2  HOOC— CH2  NH(H  HO)OC— CH2 

Glycine  Glycyl  glycine 

Amino  acetic  acid  Di-peptide  of  amino 

(2  mol.)  acetic  acid. 

(-H— OH        CH2— CO— NH 
NH— OC— CH2 

Glycine  anhydride 

Amino  acetic 
acid  anhydride 

This  formation  of  single  and  double  anhydrides  from  two  molecules 
of  an  amino  acid  by  loss  of  first  one  and  then  a  second  molecule  of  water 
is  exactly  analogous  to  the  similar  formation  of  anhydrides  in  the  case 
of  hydroxy  acetic  acid  and  all  alpha  hydroxy  acids  (p.  241). 

This  dipeptide  bears  to  amino  acetic  acid  a  relationship  similar  to 
that  which  aceto  acetic  acid  bears  to  acetic  acid.  This  is  indicated  by 
the  name  amino  aceto  amino  acetic  acid.  Another  method  of  preparing 
the  polypeptides  is  by  the  action  of  the  acid  chloride  of  the  amino  acid 
on  the  amino  acid  itself. 

(-HC1) 
CH2(NH2)— CO— (Cl    +    H)HN— CH2— COOH 

Glycyl  chloride  Glycine 

Amino  acetyl  chloride  Amino  acetic  acid 

CH2(NH2)— CO— NH— CH2— COOH 

Glycyl  glycine 

In  the  list  of  amino  acids  which  follows  there  are  included  all  that 
have  been  obtained  as  products  of  protein  hydrolysis  and  which  are 
therefore  necessary  to  consider  in  connection  with  the  constitution 
of  proteins.  Most  of  them  are  derivatives  of  acids,  which  we  have 
already  studied  though  several  of  them  contain  cyclic  or  benzene 
groups  derived  from  compounds  which  we  shall  take  up  in  Part  II. 


388  ORGANIC  CHEMISTRY 

It  will  be  unnecessary  to  give  the  properties  or  the  derivatives  of  the 
different  acids  except  in  a  few  cases  where  the  derivatives  are  individ- 
ually important.  The  general  facts  which  have  just  been  discussed 
apply  to  all. 

I.  MONO-AMINO  ACIDS  DERIVED  FROM  MONO-BASIC  ACIDS 
Glycine,  CHa(NH2)— COOH,  Amino  Acetic  Acid 

This  acid  is  also  called  glycocoll  but  the  name  glycine  is  better  as  it 
indicates  the  amine  character  of  the  compound.  The  termination 
ine  has  been  generally  accepted  for  the  names  of  all  amino  acids.  A 
few  derivatives  of  glycine  are  important. 

Sarcosine,  CH2(NHCH3)— COOH,  Methyl  amino  acetic  acid,  is 
the  mono-methyl  derivative.  It  is  obtained  from  natural  substances, 
viz.,  from  creatine,  found  in  muscular  tissue,  and  from  caffeine,  found 
in  coffee. 

Betaine  is  the  tetra-methyl  ammonium  inner  salt  compound  already 
referred  to  (p.  386).  It  is  really  a  tri-methyl  derivative  of  glycine. 

^.N=(CH,)8 

CH<  ^ 


COOH 

Glycine 


It  is  found  in  the  beet-root  and  remains  in  beet  sugar  molasses.  It 
is  the  source  for  the  commercial  preparation  of  tri-methyl  amine  which 
it  yields  on  distillation.  It  will  be  referred  to  again  in  connection  with 
the  alkaloids  (Pt.  II). 

Hippuric  acid,  (C6H5— CO)— NH— CH2— COOH,  Benzoyl  glycine, 
is  a  normal  constituent  of  urine,  being  abundant  in  that  of  herbivorous 
animals  but  present  in  smaller  amounts  in  man.  It  is  a  benzoyl  deriva- 
tive of  glycine,  benzoyl  being  the  acyl  group  of  a  benzene  acid  known 
as  benzoic  acid,  (C6H5— CO)OH. 

It  is  similar  in  its  constitution  to  a  dipeptide  except  that  one  acid 
constituent  has  no  amino  group.  A  compound  exactly  analogous  to 
it  is  aceto  amino  acetic  acid,  CH3— CO— NH— CH2— COOH.  Such 
semi-peptides  result  when  an  amino  acid  is  treated  with  the  acid  chloride 
of  a  non-amino  acid  analogous  to  the  second  method  of  preparing  poly- 


AMINO   ACIDS  389 

peptides  (p.  387).     In  urine  it  is  formed  from  benzoic  acid  in  the  food 
and  glycine  resulting  from  the  breaking  down  of  protein  in  the  body. 

Di-amino  Acetic  Acid,  CH(NH2)2— COOH 

This  acid  has  also  been  obtained  as  a  hydrolytic  product  of  proteins. 
Alanine,  CH3— CH(NH2)— COOH,  a-Amino  Propionic  Acid 

The  next  higher  acid  to  acetic,  viz.,  propionic  acid,  yields  an  alpha- 
ammo  acid  known  as  alanine.  There  has  also  been  isolated  from  mus- 
cle a  beta-ammo  propionic  acid,  CH2(NH2) — CH2 — COOH. 

Serine,  CH2(OH)— CH(NH2)— COOH,  a-Amino  /3-Hydroxy  Propionic  Acid 

This  acid  is  obtained  from  silk  protein.     It  is  also  called  hydroxy 
alanine. 
Cysteine,  CH2(SH)— CH(NH2)— COOH,  a-Amino  0-Sulph -hydro  Propionic  Acid 

This  acid  is  the  sulphur  analogue  of  serine. 

Cystine,  HOOC— CH(NH2)— CH2— S— S—CH2— CH(NH2)— COOH 

This  acid  is  a  di-cysteine  resulting  from  two  molecules  of  cysteine 
by  the  loss  of  two  hydrogen  atoms  from  the  sulph-hydro  groups,  ( — SH). 
It  is  found  in  urinary  calculi. 

Phenyl  Alanine,  C6H5— CH2— CH(NH2)— COOH,   a-Amino  /3-Phenyl  Propionic 

Acid 

This  amino  acid,  as  its  name  indicates,  is  the  phenyl  derivative  of 
alanine.  The  radical  phenyl,  (C6H0 — ),  is  from  the  hydrocarbon 
benzene,  C6H6. 

Tyrosine,    (C6H4OH)— CH2— CH(NH2)— COOH,    a-Amino  0- (Hydroxy -phenyl) 

Propionic  Acid 

This  acid  is  closely  related  to  the  preceding  one.  It  is  hydroxy- 
phenyl  alanine,  the  group  ( — C6H4OH)  being  substituted  in  the  beta 
carbon  group  of  alanine.  Tyrosine  is  of  especial  interest  as  it  was  one 
of  the  first  amino  acids  to  be  obtained  from  proteins.  It  can  be  easily 
obtained  from  cheese. 

Tryptophane,    (C8H6N)— CH2— CH(NH2)— COOH,   a-Amino    0-Indol  Propionic 

Acid 

This  is  an  amino  acid  the  name  of  which  does  not  have  the  ine 
termination.  The  beta  carbon  group  in  alanine  has  substituted  in  it  the 
complex  group,  (C8H6N),  which  is  known  as  the  indol  radical.  Indol  is 
a  benzene  derivative  related  to  indigo.  Tryptophane  derives  its  name 


3QO  ORGANIC  CHEMISTRY 

from  the  fact  that  it  was  first  obtained  in  the  digestive  products  of 
protein  by  trypsin,  the  proteolytic  enzyme  of  the  pancreatic  juice. 

Histidine,  (C3H3N2)— CH2—  CH(NH2)— COOH,  a-Amino   /3-Imidazol  Propionic 

Acid 

This  is  another  amino  acid  containing  a  cyclic  radical  substituted  in 
the  beta  carbon  group  of  alanine. 

a-Amino  Butyric  Acid,  CH3— CH2— CH(NH2)— COOH 

This  amino  acid  is  the  only  one  which  is  a  derivative  of  butyric  acid, 
the  four  carbon  member  of  the  fatty  acid  series.  It  has  no  special 
name. 

Valine,  CHs— CH— CH(NH2)— COOH,  a-Amino  Iso-valeric  Acid 

CH3 

Iso-valeric  acid  is  one  of  the  isomeric  five  carbon  acids.     It  is  3- 
methyl  butanoic  acid.     Valine  is  the  alpha-ammo  derivative  of  it. 
a-Amino  Valeric  Acid,  CH3— CH2— CH2— CH(NH2)— COOH 

There  has  also  been  isolated  from  the  products  of  protein  hydro- 
lysis the  alpha-ammo  derivative  of  the  normal  five  carbon  acid,  valeric 
acid.  It  has  no  special  name. 

Leucine,  CHs— CH— CH2— CH(NH2)— COOH,  a-Amino  /3-Iso-propyl  Propionic 

Acid 
CH3 

The  amino  acid  leucine  is  an  alpha-ammo  derivative  of  one  of  the 
other  isomeric  six  carbon  acids,  viz.,  ^-methyl  pentanoic  acid,  as  is  shown 
in  the  above  formula. 

Iso-leucine,  (CHs— CH2)— CH— CH(NH2)— COOH,  a-Amino  /3-Efhyl  0-Methyl 

Propionic  Acid 
CH3 

This  amino  acid,  as  the  name  indicates,  is  isomeric  with  leucine.  It  is 
the  alpha-ammo  derivative  of  another  of  the  isomeric  six  carbon  acids, 
viz.,  3 -methyl  pentanoic  acid. 

Caprine,    Glyco-leucine,    CH3— CH2— CH2— CH2— CH(NH2)— COOH,    a-Amino 

Caproic  Acid 

Caprine  is  the  alpha-ammo  derivative  of  the  normal  six  carbon  acid 
or  caproic  acid.  Its  name  glyco-leucine  indicates  its  relation  to  glu- 
cose and  to  leucine. 


AMINO   ACIDS  391 

II.  DI-AMINO  ACIDS  DERIVED  FROM  MONO-BASIC  ACIDS 

Arginine,  (H2N—  C(NH)— NH)— CH2— CH2— CH2— CH(NH2)— COOH,  a-Amino 
5-Guanidine  Valeric  Acid 

Arginine  and  lysine  are  amino  acids  which  differ  from  those  pre- 
ceding in  having  two  amino  groups.  In  arginine  one  of  the  amino 
groups  is  part  of  a  complex  radical  of  a  compound  known  as  guanidine, 
H2N — C(NH)— NH2,  which  is  related  to  urea  and  will  soon  be  dis- 
cussed. Arginine  is  a  derivative  of  the  normal  five  carbon  acid  known 
as  valeric  acid  having  one  amino  group  in  the  alpha  position  and  the 
guanidine  radical,  containing  the  second  amino  group,  in  the  end  carbon 
group  or  delta  position. 

Lysine,  CH2(NH2)— CH2— CH2— CH2— CH(NH2)— COOH,  a-e-Di-amino  Caproic 

Acid 

The  other  di-amino  acid  derived  from  mono-basic  acids  is  known  as 
lysine.  It  corresponds  to  the  mono-amin'o  acid,  glyco-leucine.  Both 
are  derived  from  the  normal  six  carbon  acid,  caproic  acid. 

III.  MONO -AMINO  ACIDS  DERIVED  FROM  DI-BASIC  ACIDS 

CH(NH2)— COOH 

Aspartic  Acid,  ,  Amino  Succinic  Acid 

CH2—      —COOH 

This  amino  acid  is  the  mono-amino  derivative  of  the  di-basic  suc- 
cinicacid. 

Asparagine  is  an  important  derivative  of  aspartic  acid.  It  is  the 
mono-acid-amide)  viz., 

CH(NH2)— COOH 

CH2—     -CO— NH2 

Asparagine  is  found  in  several  plants,  especially  in  asparagus,  from 
which  both  it  and  aspartic  acid  derive  their  names.  While  it  contatns 
two  amino  groups  it  is  not  a  di-amine  as  one  amino  group  is  in  the  acid 
amide  grouping. 

Glutamine,  Glutaminic  Acid,  HOOC— CH2— CH2— CH(NH2)— COOH,  a-Amino 

Glutaric  Acid 

The  next  higher  di-basic  acid  to  succinic  acid,  viz.,  glutaric  acid, 
yields  an  amino  acid  known  as  glutamine,  glutaminic  acid,  or  glutamic 
acid.  It  occurs  more  widely  distributed  than  any  of  the  other  amino 
acids.  Most  proteins  yield  larger  amounts  of  it  than  of  any  other 


392  ORGANIC  CHEMISTRY 

amino  acid.    In  the  group  of  proteins  known  as  protamines  it  is  wholly 
absent  in  the  hydrolytic  products. 

Proline,  C4H8N— COOH,  a-Pyrrolidine  Carboxylic  Acid 

This  compound  is  not  a  simple  amino  acid  but  is  a  carboxyl  deriva- 
tive of  a  five  membered  cyclic  compound,  containing  an  ( — NH — ) 
group,  known  as  pyrrolidine  (p.  194  and  Part  II). 
Oxy-proline,  (C4H7(OH)N)— COOH,  <*-(Hydroxy  Pyrrolidine)  Carboxylic  Acid 

As  its  name  indicates  oxy-proline  is  an  hydroxy  derivative  of  proline. 
The  position  of  the  hydroxyl  group  in  the  pyrrolidine  ring  is  not  known. 

Di-amino  Di-hydroxy  Suberic  Acid,  C8Hi6N2O6 
Di-amino  Tri-hydroxy  Dodecanoic  Acid,  C^Hge^Os 

These  two  amino  acids  can  be  given  by  name  and  empirical  formula 
only,  as  their  full  constitution  is  unknown.  The  first  is  a  derivative  of 
the  eight  carbon  di-basic  acid  known  as  suberic  acid,  HOOC — (CH2)6— 
COOH.  The  second  is  derived  from  the  twelve  carbon  mono-basic 
acid,  dodecanoic  acid,  CH3(CH2)i0—  COOH. 

The  foregoing  description  is  little  more  than  a  catalogue  list  but  it 
shows  that  the  amino  acids  related  to  proteins  are  in  most  cases  deriva- 
tives of  well  known  mono-  and  di-basic  aliphatic  acids  and  that  at  least 
one  nitrogen  in  every  case  except  in  proline  and  oxy-proline  is  in  the 
form  of  a  simple  amino  group  substituted  in  the  acid,  usually  in  the  alpha 
position.  Six  of  the  number  contain  also  more  or  less  complex  cyclic 
groups  substituted  in  the  aliphatic  acid  and  four  of  these  cyclic  groups 
contain  nitrogen  in  the  imino  grouping  (  =  NH).  Proline  and  oxy-pro- 
line have  no  simple  amino  group.  Taken  as  a  whole,  therefore,  both  as 
to  their  number  and  constitution,  the  amino  acids  form  a  rather  complex 
group  and  indicate  how  complex  must  be  the  constitution  of  the  proteins 
from  which  they  are  derived.  More  detailed  discussion  of  the  proper- 
ties of  the  individual  acids  and  the  amounts  in  which  they  are  obtained 
by  the  hydrolysis  of  different  proteins  may  be  found  in  larger  books  on 
biochemistry  and  physiological  chemistry. 

B.  PROTEINS 

Proteins  like  fats  and  carbohydrates  are  substances  of  great  biolog- 
ical importance.  All  three  are  esesntial  organic  constituents  of  every 
living  cell.  The  most  common  examples  of  proteins  are  such  substances 
as  the  white  of  egg,  egg  albumin;  the  gummy  substance  in  wheat, 


PROTEINS 


393 


wheat  gluten ;  and  the  curd  of  milk,  casein.  The  chemical  term  pro- 
tein has  a  similar  significance  to  the  biological  term  protoplasm  for  both 
names  have  reference  to  the  primary  or  fundamental  nature  of  the 
substances,  protein  meaning  to  be  first  and  protoplasm  first  form.  The 
two  are  not,  however,  synonymous  or  equivalent  terms  for  it  has  been 
shown  that  while  protein  is  an  essential  constituent  of  cell  protoplasm 
it  is  not  the  only  one,  for  both  carbohydrates  and  fats,  together  with 
certain  inorganic  salts,  are  also  always  present.  Biologically,  therefore, 
fats,  carbohydrates  and  proteins  are  of  similar  importance  and  we  can- 
not say  tht  one  is  more  essential  to  living  matter  than  the  other  two. 

In  the  development  of  our  knowledge  of  the  chemistry  of  these 
biological  compounds  both  the  fats  and  carbohydrates  were  pretty 
thoroughly  understood  long  before  the  proteins.  It  has  been  found 
that  in  their  constitution  the  fats  are  relatively  simple,  the  carbo- 
hydrates considerably  more  complex  and  the  proteins  the  most  complex 
of  all.  In  connection  with  our  discussion  of  the  constitution  of  the 
carbohydrates  we  stated  that  Emil  Fischer  was  one  of  the  foremost 
of  the  workers  in  this  field  and  the  one  who  first  synthesized  a  member 
of  the  hexose  mono-saccharose  group  (p.  340).  It  is  especially  inter- 
esting that  one  who  did  so  much  to  establish  our  knowledge  of  one 
group  of  the  essential  constituents  of  living  matter  should  later  turn 
his  attention  to  the  remaining  unsolved  constituent  and  in  a  most 
wonderful  way  clear  up  the  whole  matter.  We  do  not  mean  that  he 
alone  solved  this  problem  for  many  others  have  made  most  important 
contributions  to  the  subject.  In  addition  to  Fischer,  the  names  of 
Conheim,  Kossel,  Kiitscher,  Thomas  B.  Osborne  of  the  New  Haven 
Experiment  Station,  and  above  all  Abderhalden,  the  student  of  Fischer 
and  co-worker  with  him,  will  always  be  associated  with  the  subject  of 
proteins  and  the  development  of  our  ideas  as  to  their  constitution. 

Composition. — Proteins  differ  from  the  other  essential  organic 
constituents  of  living  cells  in  containing  not  only  carbon,  hydrogen 
and  oxygen  as  carbohydrates  and  fats  do,  but  in  addition  to  this  they 
always  contain  the  element  nitrogen;  usually  sulphur  and  sometimes 
phosphorus,  or  iron,  or  one  of  a  few  other  elements.  The  proportion 
of  nitrogen  in  proteins  is  fairly  constant,  varying  between  the  approxi- 
mate limits  of  15  per  cent  and  19  per  cent  while  in  most  cases  it  ap- 
proximates closely  the  value  of  16  per  cent.  This  was  one  of  the  first 
facts  noted  in  regard  to  proteins  and  has  given  rise  to  the  universal 


394  ORGANIC  CHEMISTRY 

use  of  the  factor  6.25  for  converting  per  cent  nitrogen  into  per  cent 
protein.  In  the  ordinary  agricultural  analysis  of  plant  and  animal 
materials  the  substance  is  analyzed  for  nitrogen,  usually  by  the  Kjeldahl 
method,  and  the  nitrogen  is  converted  into  protein  by  means  of  this 
factor.  N.  (per  cent)  X  6.25  =  Protein  (per  cent).  In  all  older  analy- 
ses of  such  substances  and  when  the  factor  is  not  otherwise  definitely 
stated  this  factor  is  understood. 

The  complete  percentage  composition  of  proteins  may  be  given  as 
follows: 

Carbon  5i~55    Per  cent 

Hydrogen         6-7      per  cent 

Nitrogen        15-19    per  cent 

Oxygen  20-24    Per  cent 

Sulphur        0.3-2.3  per  cent 

Phosphorus  0.4-0.8  per  cent  (when  present) 

Other  elements,  traces  only  (when  present) 

Molecular  Weight. — While  the  composition  of  proteins  has  been 
accurately  determined  it  is  impossible  as  yet  to  assign  a  molecular 
formula  because  in  order  to  do  this  we  must  know  the  molecular  weight, 
and  accurate  or  even  acceptable  molecular  weights  have  not  yet  been 
obtained.  Every  indication  points  to  the  view  that  the  compounds 
are  both  exceedingly  complex  in  structure  and  exceptionally  large  in 
their  molecular  weight.  Assuming,  in  the  case  of  sulphur,  iron,  or 
one  of  the  other  elements,  which  are  present  in  very  small  percentage 
amounts,  that  at  least  one  atom  of  the  particular  element  is  present  in 
the  molecule,  we  can  calculate  the  size  of  the  molecule.  Determina- 
tions made  in  this  way  have  given  results  as  follows: 

Edestin,  based  on  per  cent  of  sulphur  present,  molecular  weight 

=  14,530 
Egg  albumin,  based  on  per  cent  of  sulphur  present,  molecular  weight 

=  15,203 

Blood  serum  albumin  (horse),  based  on  per  cent  of  sulphur  present, 

molecular  weight  =   14,989 

Blood  oxy-hemoglobin   (horse),   based  on   per    cent    of    sulphur 

present,  molecular  weight  =  16,655 

Blood  oxy-hemoglobin,  based  on  per  cent^  of  sulphur  and  iron 

present,  molecular  weight  =  15,000 


PROTEINS  395 

A  molecular  formula  for  oxy-hemoglobin  based  upon  its  percentage 
composition  and  the  molecular  weight  as  given  in  the  last  figure,  viz., 
15,000,  is 

C«6&HmiOai4NmSiFe  Oxy-hemoglobin 

Such  a  formula  of  course  means  little  except  to  emphasize  the  fact 
that  we  are  dealing  with  compounds  of  very  large  molecular  weight 
and  consequently  of  very  complex  structure  seeing  that  the  elements 
present  are  few  and  of  relatively  small  mass. 

Physical  Properties. — The  physical  properties  of  the  proteins 
were  the  first  basis  for  classifying  them  into  various  related  groups  and 
for  a  long  time  remained  our  only  basis  for  such  classification. 

Non-crystalline. — -The  fact  that  proteins  are  non-crystalline  sub- 
stances has  made  the  preparation  of  pure  individual  compounds  practi- 
cally impossible.  We  are  therefore  unable  to  say  whether  any  so- 
called  individual  protein  is  a  true  chemical  individual  or  not. 

Solubility. — The  only  physical  property  which  at  first  gave  any 
indication  that  individual  compounds  were  obtained  is  that  of  solu- 
bility, and  here  too  the  line  of  demarkation  between  two  proteins  is 
often  very  indistinct,  as  differences  in  solubility  are  not  sharp,  as  is 
often  the  case  with  crystalline  compounds.  Differences  in  solubility 
in  such  reagents  as  water,  alcohol,  neutral  salt  solutions  of  different 
concentrations,  dilute  alkalies,  etc.,  were  the  basis  for  the  first  separa- 
tion of  the  proteins  into  groups.  For  example,  certain  proteins  like 
egg  albumin  were  found  to  differ  from  all  others  in  being  soluble  in  water, 
and  proteins  of  similar  solubility  found  in  blood  and  milk  were  termed 
blood  albumin  and  milk  albumin.  Proteins  of  another  group  were 
found  to  be  soluble  in  dilute  neutral  salt  solutions  but  insoluble  in  water; 
others  were  soluble  in  alcohol;  etc.  This  illustrates  the  way  in  which 
names  and  groups  became  fixed. 

Chemical  Properties. — In  their  chemical  properties  the  proteins 
are  characterized  by  marked  inactivity.  Largely  on  account  of  this 
property,  which  prevented  their  study  by  the  usual  methods,  practi- 
cally nothing  was  known  for  a  long  time  as  to  their  real  chemical 
nature.  Recently  the  study  of  the  decomposition  products  obtained 
by  boiling  with  acids,  i.e.,  the  hydrolytic  products,  has  led  to  the  true 
understanding  of  them. 

Amino  Nitrogen. — It  was  very  early  recognized  that  in  proteins  the 
nitrogen  was  probably  held  in  ammonia  groupings,  i.e.,  in  amino,  imino 


396  ORGANIC  CHEMISTRY 

or  acid  amide  groups  and  possibly  also  as  ammonium  salts.  Proteins 
differ  as  to  the  proportion  of  the  total  nitrogen  which  is  liberated  by 
boiling  with  magnesium  hydroxide  or  with  sodium  hydroxide  and 
the  action  of  these  different  reagents  indicates  the  proportion  of  each 
of  the  several  different  nitrogen  groupings.  Magnesium  hydroxide 
was  believed  to  set  free  as  ammonia  only  such  nitrogen  as  exists  in  the 
form  of  an  ammonium  salt.  On  the  other  hand,  sodium  hydroxide 
decomposes  ordinary  amino  acids  and  acid  amides  so  that  nitrogen  ob- 
tained as  ammonia  by  such  treatment  was  considered  as  amino  acid  or 
acid  amide  nitrogen.  Finally  decomposition  with  sulphuric  acid  and 
subsequent  distillation  with  sodium  hydroxide  converts  all  protein 
nitrogen  into  ammonia,  or  in  addition  to  that  obtained  by  the  first  two 
reagents  it  yields  also  the  strongly  basic  di-amino  nitrogen.  As  a  result 
of  this  method  of  study  the  idea  became  more  generally  accepted 
that  the  probable  combination  of  the  nitrogen  of  proteins  is  as 
amino  nitrogen  in  its  different  forms  and  usually  in  that  of  an 
amino  acid. 

Hydrolysis  of  Proteins. — Then  it  was  found  that  by  boiling  proteins 
with  dilute  acids  certain  of  the  simpler  amino  acids  were  obtained  as 
final  hydrolytic  products.  This  led  to  the  study  of  proteins  in  respect 
to  the  various  amounts  of  the  different  amino  acids  which  are  obtained 
on  hydrolysis.  For  example,  gliadin,  one  of  the  proteins  of  wheat 
gluten,  yields  an  exceedingly  large  amount,  43.66  per  cent  of  glutamine 
and  only  3.16  per  cent  of  arginine;  while  salmine  yields  no  glutamine 
but  a  very  large  amount,  89.20  per  cent,  of  arginine. 

Simple  Proteins. — Proteins  have  also  been  grouped  according  to 
the  apparent  complexity  of  the  molecule.  Certain  ones  like  the  al- 
bumins seem  to  possess  a  simpler  character  than  others  and  are  there- 
fore called  simple  proteins. 

Conjugated  Proteins. — Another  group  of  proteins  show  a  more 
complex  character  in  that  some  react  both  as  proteins  and  also  as  car- 
bohydrates. Others  show  the  presence  of  nucleic  acid,  or  iron  or  phos- 
phorus in  addition  to  the  protein.  Such  proteins  are  termed  conjugated 
proteins,  e.g.,  mucin,  a  protein  of  the  saliva,  is  a  conjugated  carbohydrate- 
protein,  or,  as  it  is  termed,  a  glyco-protein.  The  hemoglobin  of  the 
blood  is  a  conjugated  iron-protein  or  hemoglobin.  Caseinogen,  the 
protein  of  milk,  which  on  coagulation  yields  curd  or  casein,  is  a  con- 
jugated phosphorus-protein  or  phospho-protein,  etc. 


PROTEINS  397 

Derived  Proteins. — Though  generally  speaking  the  proteins  are  in- 
active compounds,  they  are  nevertheless  changed  when  acted  upon  by 
water,  dilute  alkalies  or  acids,  and  products  are  obtained  still  possessing 
protein  characters,  but  different  from  the  original  proteins  and  in  some 
cases  evidently  simpler  in  character.  These  are  termed  derived  pro- 
teins. They  are  of  several  sub-groups.  (A)  Primary  derived  proteins, 
viz.,  (i)  proteans,  derived  from  proteins  by  the  simple  action  of  water; 
(2)  meta  proteins,  derived  from  proteins  by  action  of  alkalies  or  acids; 
and  (3)  coagulated  proteins,  derived  from  proteins  by  action  of  heat, 
e.g.,  coagulated  egg  albumin.  (B)  Secondary  derived  proteins,  obtained 
by  the  action  of  enzymes  and  by  acid  hydrolysis.  These  are:  (i) 
proteoses  and  peptones,  which  are  partial  digestion  products  of  pro- 
teins by  proteolytic  enzymes;  and  (2)  peptides  or  poly-peptides,  the 
result  of  more  complete  enzymatic  or  acid  hydrolysis. 

Classification. — As  a  result  of  the  study  of  proteins  both  as  to  their 
physical  properties,  especially  solubility  and  as  to  their  decomposition 
by  acid  hydrolysis,  a  classification  of  the  so-called  individual  proteins 
has  been  accomplished. 

Common  Proteins. — Before  giving  the  classification  it  may  be 
well  simply  to  mention  some  of  the  more  common  proteins  with  the 
material  from  which  they  are  obtained : 

Egg  albumin  is  white  of  egg. 

Blood  albumin  and  milk  albumin  are  similar  proteins  obtained  from 
the  substances  indicated. 

Blood  serum  globulin,  egg  globulin,  milk  globulin  and  plant  glob- 
ulins, such  as  edestin  from  hemp  seed  and  excelsin  from  Brazil  nut, 
are  related  proteins  from  the  sources  indicated. 

Glutenin  and  gliadin  are  the  two  principal  proteins  in  wheat  to 
which  the  formation  of  the  gluten  is  due. 

Zein,  in  maize,  and  hordein,  in  barley,  are  similar  to  gliadin. 

Collagen  is  the  protein  constituent  of  connective  tissue  such  as 
tendons;  elastin  is  in  ligaments  and  keratin  is  in  epithelial  tissue,  such 
as  hoofs,  hair,  horn,  etc. 

Globin  is  the  protein  part  of  the  conjugated  protein  hemo-globm 
of  the  blood. 

Salmine,  sturine,  etc.,  are  simple  proteins,  probably  the  simplest 
of  all,  and  are  found  in  fish  sperm,  e.g.,  in  salmon  sperm  (salmine)7 
and  in  sturgeon  sperm  (sturine),  etc. 


398  ORGANIC  CHEMISTRY 

Caseinogen  is  the  principal  protein  of  milk  to  which  the  formation 
of  the  curd  is  due. 

Ovo-vitellin  is  a  similar  protein  in  egg  yolk. 

Hemo-globin  is  the  conjugated  iron-protein  constituent  of  red 
blood  corpuscles  or  really  of  the  coloring  matter  of  the  corpuscles. 

Classification  of  Proteins 
I.  Simple  Proteins 

1.  Albumins:  egg  albumin,  blood  albumin,  milk  albumin,  and  plant 

albumins. 
Soluble  in  water  and  coagulated  by  heat. 

2.  Globulins:  egg  globulin,  edestin,  excelsin. 

Insoluble  in  water,  soluble  in  dilute  neutral  solutions  of  salts 
of  strong  bases  and  strong  acids,  e.g.,  NaCl,  (NH4)2S04, 
MgS04. 

3.  Glutelins:  glutenin. 

Soluble  in  dilute  alkalies  or  acids.     Insoluble  in  all  neutral  solvents. 

4.  Prolamins :  gliadin,  zein,  hordein. 

Soluble  in  70-80  per  cent  alcohol.  Insoluble  in  water,  absolute 
alcohol  or  neutral  salt  solutions. 

5.  Albuminoids:  collagen,  elastin,  keratin. 

Insoluble  in  all  neutral  solvents. 

6.  Histones:  globin  (from  hemoglobin). 

Basic  proteins  soluble  in  water  and  dilute  acids,  insoluble  in 
ammonia.  Yield  a  large  number  of  amino  acids,  especially 
basic  or  di-amino  acids. 

7.  Protamines  :  salmine,  sturine. 

.The  simplest  of  all  proteins,  strongly  basic,  soluble  in  water,  yield 
few  amino  acids. 

II.  Conjugated  Proteins 

8.  Nucleo-proteins :  cyto-globulin,  nucleo-histone. 

Contain  nucleic  acid  and  protein. 

9.  Glyco-proteins :  mucin. 

Contain  carbohydrate  and  protein. 
10.  Phospho-proteins :  caseinogen,  ovo-vitellin. 

Contain  a  phosphorus  compound  and  protein.  The  phosphorus 
compound  is  other  than  nucleic  acid  or  lecithin. 


PROTEINS  399 

EX* 


Hemo-globins :  Hemoglobin  (from  blood). 
Contain  an  iron  compound  and  protein. 
.  Lecitho-proteins :  contain  lecithin  and  protein. 


III.  Derived  Proteins 
(^4)  Primary 

13.  Proteans:  myosah,  edestan. 

These  are  obtained  from  proteins  by  the  action  of  water,  very 
dilute  acids  or  enzymes.  Insoluble  in  water. 

14.  Meta  proteins :  alkali-albuminates,  acid-albuminates. 

Obtained  from  proteins  by  the  further  action  of  dilute  alkalies 
or  acids.  Soluble  in  water  plus  the  reagent. 

15.  Coagulated  proteins :  coagulated  egg  albumin. 

Obtained  from  proteins  by  the  action  of  heat  or  alcohol. 
Insoluble. 

(B)  Secondary 

Product  of  proteolytic  hydrolysis  or  digestion  of  proteins,  also  by  acid 
hydrolysis. 

1 6.  Proteoses: 

Soluble  in  water  and  not  coagulated  by  heat.  Precipitated  from 
solution  by  saturating  it  with  ammonium  sulphate,  (NH4)2SO4 
or  zinc  sulphate,  ZnSO4. 

17.  Peptones: 

Soluble  in  water,  not  coagulated  by  heat  and  not  precipitated 
from  solution  by  saturation  with  ammonium  sulphate  solution. 

1 8.  Peptides  or  poly-pep  tides : 

These  are  not  really  proteins  at  all  but  are  compounds  of  defi- 
nitely known  constitution  and  which  may  also  be  formed  by 
joining  together  two  or  more  amino  acids  in  the  form  of  single 
anhydrides  (p.  386). 

POLY-PEPTIDES  AND  THE  CONSTITUTION  OF  PROTEINS 

There  remains  to  be  considered  the  relation  of  the  poly-peptides  to 
the  proteins  and  the  probable  constitution  of  the  proteins.  The  study 
of  proteins  on  which  the  above  classification  is  based  has  been  almost 
wholly  that  of  their  composition  and  physical  properties. 


400  ORGANIC  CHEMISTRY 

Analytical  and  Synthetical  Study  of  Proteins. — Fischer  attacked 
the  problem  of  the  constitution  of  proteins  from  the  synthetic  side. 
Assuming  that  proteins  consist  of  units  of  amino  acids,  as  indicated 
by  the  analytical  study  of  their  hydrolytic  products,  he  attempted  to 
synthesize,  from  amino  acids,  compounds  of  similar  complexity  to  the 
proteins.  As  already  stated  (p.  386),  he  found  that  the  double  an- 
hydrides, resulting  from  the  esters  of  amino  acids  by  the  loss  of  two 
molecules  of  alcohol  from  two  molecules  of  the  ester,  took  up  one  mole- 
cule of  water  when  treated  with  dilute  alkali  and  a  single  anhydride 
was  obtained.  The  reactions  may  be  represented  as  follows: 

— 2R— OH 
CH3— CH— CO— (OR  H)NH  — > 

HN(H  RO)— OC— CH— CH3 

Alanine  (ester) 
(2  mol.) 

CH,— CH— CO— NH 


NH— OC— CH— CH3 
Alanine  anhydride 

(double  anhydride) 

+  H2O  (dilute  alkali) 
CH3— CH— CO NH  or          CH3— CH(NH2)— CO— NH— CH— COOH 

NH2  HOOC— CH— CH3  CH3 

Alanyl  alanine 

Di-peptide  (single  anhydride) 

Alanyl  Alanine. — From  these  reactions  the  resulting  compound 
must  have  the  constitution  of  a  single  anhydride  which  would  be  formed 
by  the  union  of  two  molecules  of  the  amino  acid  through  the  loss  of  one 
molecule  of  water,  the  hydroxyl  coming  from  the  carboxyl  group  of  one  acid 
and  the  hydrogen  from  the  amino  group  of  the  other  acid.  These  compounds 
he  termed  peptides  or  poly-peptides.  The  one  illustrated  above  is  a  di- 
peptide  formed  from  two  molecules  of  alanine,  a-amino  propionic  acid. 
It  is  called  specifically  alanyl  alanine.  In  a  wonderfully  productive 
series  of  investigations  he  found  that  a  third  amino  acid  can  be  linked 
to  the  di-peptide,  through  the  remaining  carboxyl  group  of  the  di- 
peptide  and  the  amino  group  of  the  new  amino  acid,  and  a  poly-peptide 
consisting  of  three  amino  acid  units,  i.e.,  a  tri-peptide,  obtained.  Also 
this  linking  on  of  a  new  amino  acid  unit  can  be  continued  and  a  large 
number  of  such  poly-peptides  actually  obtained  containing  all  the  way 


PROTEINS  401 

from  two  to  eighteen  amino  acid  units.     These  amino  acid  units  may  be 
alike,  as  in  the  case  just  given,  or  different,  e.g., 
CH2(NH2)  — CO— NH— CH— COOH 

and 
CH3 

Glycyl  alanine 

CH3— CH(NH2)— CO— NH— CH2— COOH 

Alanyl  glycine 

Glycyl  Alanine.  Alanyl  Glycine. — It  will  be  seen  at  once  that  a 
large  number  of  polypeptides  are  possible  of  formation  from  the  amino 
acids  which  are  known  and  which  have  been  obtained  as  products  of 
protein  hydrolysis. 

alpha-Ammo  Acids. — Two  things  are  prominent  in  considering  the 
amino  acids  which  have  been  obtained  as  hydrolytic  products  of  pro- 
teins. First,  these  amino-acids  are,  in  every  case  except  one,  alpha- 
amino  acids  and  many  of  them  are  derivatives  of  alpha-amino  pro- 
pionic  acid.  The  formation  of  poly-peptides  is  therefore  natural,  as 
these  have  the  constitution  of  the  particular  form  of  anhydride  that  is 
characteristic  of  #/^a-hydroxy  and  alpha-amino  acids  in  general 
(P-  3^7).  Second,  all  of  the  amino  acids,  with  the  exception  of 
glycine,  contain  an  asymmetric  carbon  atom. 

Stereo -isomers. — The  compounds  thus  possess  stereo-isomerism  and 
exist  in  the  three  forms,  viz.,  dextro  (d),  lew  (/),  and  racemic  or  inactive 
(t).  In  most  cases  all  three  of  these  isomers  are  known.  We  can  rea- 
lize at  once  the  exceeding  large  variety  of  poly-peptide  combinations 
which  are  possible  among  the  twenty  or  more  amino  acids  when  these  are 
combined  in  proportions  ranging  from  di-peptides  of  two  amino  acids 
up  to  octa-deca-peptides  of  eighteen  amino  acids.  Each  one  of  the 
stereo-isomers  of  each  amino  acid  can  also  form  a  poly-peptide  union 
with  itself  or  with  any  other  and  also  in  each  case  the  grouping  of  any 
two  may  be  reversed  as  illustrated  by  the  two  di-peptides  formed  from 
glycine  and  alanine,  viz.,  glycyl  alanine  and  alanyl  glycine.  The 
complexity  of  the  molecule  and  the  possibilities  of  isomeric  groupings 
may  be  illustrated  with  the  eighteen  amino  acid  poly-peptide,  the  octa- 
deca-peptide,  which  has  been  synthetically  prepared.  It  is  composed 
of  three  levo-leucine  units,  (CH3)2  =  CH— CH2— CH(NH2)— COOH,  or 
H2N— CH— COOH,  and  fifteen  glycine  units,  CH2(NH2)— COOH. 

C4H9 

26 


402  ORGANIC  CHEMISTRY 

The  following  formula  represents  the  grouping  of  these  eighteen  amino 
acid  units  as  established  by  the  synthesis  of  the  compound. 

H2N— CH— CO HN— CH2— CO HN— CH2— CO HN- 

C4H9 
CH2— CO HN— CH— CO HN— CH2— CO NH— CH2— 

C4H9 
CO HN— CH2— CO HN— CH— CO HN— CH2— CO— 

C4H9 

HN— CH2— CO HN— CH2— CO HN— CH2— CO HN- 

CH2— CO HN— CH2— CO—  -HN— CH2— CO HN— CH2— 

CO HN— CH2— COOH 

l-Leucyl  tri-glycyl  1-leucyl  tri-glycyl  1-leucyl  octa-glycyl  glycine 

Octa-deca-peptide  Mol.  wt.  =  1213.3 

In  this  compound  we  have  a  substance  approaching  the  proteins  in 
complexity  and  it  has  been  found  to  resemble  the  proteins  and  the 
proteoses  and  peptones  in  its  physical  properties.  Furthermore,  a 
simpler  synthetic  poly-pep  tide,  viz.,  a  tetra-peptide,  has  been  found  to  be 
almost  identical  with  an  isomeric  poly -pep  tide  obtained  by  the  hydroly- 
sis of  a  silk  protein.  This  synthetic  tetra-peptide  has  the  following 
constitution : 

H2N— CH2— CO HN— CH— CO — HN— CH2— CO— HN— CH— COOH 

I 

CH3  CH2— C6H4OH 

Glycyl  d-alanyl  glycyl  1-tyrosine 

Tetra-peptide  (synthetic) 

We  can  easily  calculate  that,  due  to  different  arrangements  of  the 
four  units,  there  are  eight  possible  isomeric  tetra-pep tides  containing 
these  same  four  amino  acids  of  the  same  stereo-isomeric  forms.  One  of 
these  eight  isomers  may  prove  to  be  actually  identical  with  the  hydrolytic 
tetra-peptide  but  it  may  be  necessary  to  wait  until  these  eight  isomers 
have  all  been  synthesized  before  we  can  state  positively  that  a  synthetic 
poly-peptide  is  identical  with  a  poly-peptide  obtained  by  the  hydrolysis  of  a 
protein.  The  probability  is  that  one  of  these  possible  synthetic  com- 
pounds will  be  found  to  be  identical  with  the  hydrolytic.  When  this  is 
done  we  shall  have  proven  that  proteins  are  poly-peptide  combinations 


PROTEINS  403 

of  alpha-amino  acids.     While  the  actual  proof  is  yet  lacking  there  is 
little  doubt  that  proteins  have  the  constitution  of  poly-peptides. 

Tautomerism  of  Poly-peptides  and  Proteins. — Certain  facts  seem 
to  indicate  that  poly-peptide  groupings  of  the  amino  acids  are  able  to 
exist  in  a  tautomeric  form  and  that  they  are  converted  into  this  form 
by  the  action  of  alkalies.  The  poly-peptides,  if  the  constitution  assigned 
them  is  true,  contain  the  same  asymmetric  carbon  atoms  as  the  amino 
acids  of  which  they  are  composed. 

H  H     O  H 

I  I      II  ] 

CH3— C— COOH  CH3— C— C— NH— C— COOH 

I  I 

NH2  NH2  CH3 

Alanine  Alanyl  alanine 

The  proteins  themselves  possess  optical  activity  thus  supporting 
the  view  of  their  poly-peptide  constitution.  Now  when  hydrolyzed 
by  enzymes  or  by  acids  the  proteins  yield  amino  acids  that  are  all 
optically  active,  i.e.,  either  dextro  or  levo.  Usually  the  total  activity 
of  the  amino  acids  obtained  is  greater  than  that  of  the  original  protein. 
Now  when  hydrolysis  of  the  protein  is  effected  by  alkalies  instead  of 
acids  or  when  the  acid  hydrolysis  is  preceded  by  treatment  of  the  protein 
with  alkalies  it  is  found  that  the  amino  acids  obtained  are  usually  of  the 
racemic  or  inactive  form,  i.e.,  there  are  equal  amounts  of  the  dextro  and 
levo  forms.  Such  racemization  by  the  action  of  alkalies  occurs  much 
more  readily  with  the  proteins  than  with  the  amino  acids  themselves 
which  indicates  that  the  polypep tide  grouping  is  involved  in  the  change. 
The  explanation  given  is  that  alkalies  effect  a  tautomeric  rearrange- 
ment of  the  poly-peptide  exactly  analogous  to  that  occurring  in  aceto- 
acetic  ester  (p.  256)  and  the  ketone  form  of  the  poly-peptide  as  in  the 
constitution  already  given  is  converted  into  the  enol  form. 
H  O  H  HO  H 

CH3 — C— C— NH— C— COOH  CH3— C  =  C— NH— C— COOH 

II  II 

NH2  CH3  NH2  CH3 

Alanyl  alanine  Alanyl  alanine 

Ketone  form  Enol  form 

In  such  a  rearrangement  one  of  the  asymmetric  carbon  atoms  loses 
its  asymmetry  and  becomes  symmetrical.  If  now  this  non-asymmetric 


404  ORGANIC  CHEMISTRY 

amino  acid  group  by  hydrolysis  of  the  poly-peptide  and  formation  of  the 
individual  amino  acid,  regains  its  asymmetric  carbon  atom  which  it 
must  possess  in  the  amino  acid  there  would  be  formed  equal  amounts  of 
the  dextro  and  levo  forms  and  the  acid  would  be  obtained  in  the  racemic 
inactive  form. 

A  study  of  the  changes  in  optical  activity  due  to  hydrolysis  also 
makes  it  possible  to  determine  which  amino  acid  group  is  at  the  end  of 
the  polypeptide  chain  as  this  amino  acid  does  not  undergo  the  above 
tautomeric  rearrangement,  as  the  asymmetry  of  the  carbon  is  not 
affected. 

HYDROLYSIS  BY  ENZYMES 

In  the  study  of  the  constitution  of  proteins  the  hydrolytic  cleavage  of 
the  protein  molecule  into  amino  acids  is  usually  accomplished  by  boiling 
with  dilute  acids.  Boiling  with  alkalies,  e.g.  barium  hydroxide,  Ba- 
(OH)2,  also  produces  hydrolysis.  We  have  also  mentioned  the  fact  that 
enzymes  hydrolyze  proteins  and  the  two  groups  of  secondary  derived 
proteins,  viz.,  proteoses  and  peptones,  are  principally  the  result  of  en- 
zymatic hydrolysis.  In  general  it  may  be  said  that  enzymatic  hydroly- 
sis of  proteins  proceeds  more  gradually  and  permits  the  easier  isolation 
of  intermediate  products  than  acid  hydrolysis.  While  the  study  of 
enzymatic  action  belongs  more  to  a  study  of  biological  chemistry  than 
to  systematic  organic,  yet  it  is  well  here,  as  in  the  case  of  carbohydrates, 
to  mention  the  enzymes  that  are  especially  important. 

Proteolytic  Enzymes. — The  enzymes  which  hydrolyze  proteins  are 
called  proteolytic  enzymes  or  proteases.  They  belong  to  the  general  class 
of  hydrolytic  enzymes.  The  more  important  representatives  are  those 
found  in  the  animal  body  which  are  involved  in  the  processes  of  food 
digestion.  The  following  may  be  mentioned  with  the  hydrolytic 
products  produced  in  normal  food  digestion.  Pepsin,  the  proteolytic 
enzyme  present  in  the  gastric  juice  of  the  stomach.  It  hydrolyzes  pro- 
teins in  the  most  part  to  proteoses,  peptones  and  peptides.  By  pro- 
longed action  or  under  artificial  conditions  pepsin  may  yield  amino 
acids  also.  Trypsin,  the  proteolytic  enzyme  present  in  the  activated 
pancreatic  juice,  hydrolyzes  proteins  in  part  to  proteoses,  peptones  and 
peptides  but  mostly  to  amino  acids.  Erepsin,  the  proteolytic  enzyme  of 
the  intestinal  juice,  hydrolyzes  protein  but  mostly  proteoses,  peptones 
and  peptides  to  amino  acids. 


PROTEINS  405 

QUALITATIVE  TESTS 

Color  Reactions. — Proteins  respond  to  certain  empirical  qualitative 
tests  made  by  means  of  reagents  some  of  which  give  color  reactions  and 
some  precipitations.  In  general  all  proteins  respond  to  the  color  tests 
and  in  some  cases  non-protein  compounds  also.  Some  of  the  color 
reactions  have  been  shown  to  be  due  to  the  presence  of  certain  groups  in 
the  protein  molecule  and  they  thus  indicate  a  differentiation  though  this 
is  not  sufficient  in  most  cases  to  be  of  much  value. 

Millon's  Reaction. — This  reaction  is  produced  by  a  reagent  known  as 
Millon's  reagent  which  contains  a  mixture  of  mercurous  nitrate  and 
nitrite  in  nitric  acid.  It  is  made  as  follows :  dissolve  one  part  by  weight 
of  mercury  in  two  parts  by  weight  of  concentrated  nitric  acid  (sp.  gr. 
1.42)  and  then  dilute  with  two  volumes  of  water.  The  test  works  best 
with  solid  proteins  and  when  to  a  little  of  the  protein  a  few  drops  of 
Millon's  reagent  is  added  and  then  warmed  a  yellow  or  white  color 
changing  to  red  indicates  protein.  The  test  is  produced  by  any  com- 
pound containing  the  hydroxy-phenyl  group,  ( — C6H4OH).  As  the 
amino  acid  tryosine,  C6H4(OH)— CH2— CH(NH2)— COOH,  is  the  only 
one  containing  this  group  the  test  will  be  given  only  by  proteins  which 
yield  this  acid  on  hydrolysis.  Gelatin  and  some  of  the  protamines  do 
not  yield  tryosine  on  hydrolysis  and  do  not  respond  to  Millon's  test. 
On  the  other  hand  certain  non-nitrogenous  compounds  like  phenol, 
C6H5— OH, 


X 
salicylic  acid,  C6H4<^  ,  and  thymol,  C6H3 

XCOOH  CH(CH3)2 

respond  to  the  test. 

Biuret  Reaction. — This  reaction  is  produced  with  solutions  of  pro- 
teins by  dilute  copper  sulphate  in  presence  of  strong  alkali.  To  a  little 
protein  solution  add  an  equal  volume  of  strong  potassium  hydroxide 
and  mix.  Add  to  this  a  few  drops  of  very  dilute  copper  sulphate  (2 
drops  10  per  cent  CuSO4  to  about  10  cc.  water).  A  pinkish  violet 
color  due  to  the  formation  of  a  copper  compound  indicates  protein. 
The  reaction  gets  its  name  from  the  fact  that  biuret,  H2N — CO — NH — 
CO — NH2,  formed  from  urea  by  the  loss  of  ammonia  from  two  molecules 
(p.  434),  responds  to  the  test.  It  is  due  to  the  presence  in  the  protein 
and  other  compounds,  of  two  amino  groups,  ( — NH2),  one  of  which  may 
have  substitution  groups  within  it,  the  two  groups  being  linked  to  differ- 


4C>6  ORGANIC  CHEMISTRY 

ent  carbon  atoms.  As  this  condition  is  present  in  any  protein  or  poly- 
peptide  all  proteins  and  derived  proteins  respond.  In  addition  to  the 
proteins,  non-protein  compounds  other  than  biuret,  such  as  oxamide, 
H2N—  CO—  CO—  NH2,  and  asparagine  H2N—  OC—  CH2—  CH(NH2) 


y 
—  COOH  give  positive  tests.     Urea,  CO\^         ,  on    the    other    hand, 

XNH2 

with  two  amino  groups  linked  to  one  carbon  atom,  does  not  respond  to 
the  test. 

Xanthoproteic  Reaction.  —  This  reaction  is  produced  by  the  action  of 
concentrated  nitric  acid  and  results  in  a  yellow  color  which  turns  orange 
on  the  addition  of  ammonium  hydroxide.  The  yellow  stain  of  nitric 
acid  on  flesh  is  due  to  £he  protein  that  is  present.  The  reaction  is 
caused  by  the  presence  of  the  phenyl  group,  (C6H5  —  ),  and  any  non- 
protein  compound  containing  this  group  also  gives  the  test. 

Hopkins-Cole  Reaction.  Glyoxylic  Acid  Reaction.  —  This  reaction 
is  produced  with  proteins  by  the  action  of  glyoxylic  acid,  CH(OH)2  — 
COOH  (p.  '252).  To  a  little  protein  solution  add  an  equal  volume  of  a 
solution  of  glyoxylic  acid  made  by  reducing  oxalic  acid  with  sodium 
amalgam.  Mix  thoroughly  and  then  introduce  an  equal  volume  of 
concentrated  sulphuric  acid  by  means  of  a  pipette  reaching  to  the 
bottom  of  the  test  tube  so  as  not  to  mix  the  acid  and  the  solution.  A 
reddish-violet  color  at  the  zone  between  the  two  liquids  shows  the 
presence  of  protein. 

Precipitation  Tests.  —  Several  reagents  possess  the  property  of 
precipitating  proteins  from  solution  as  unchanged  protein. 

Precipitated  Protein.  —  Ammonium  sulphate,  when  added  to  satura- 
tion, precipitates  from  solution  all  proteins  and  derived  proteins  except 
peptones.  Sodium  chloride  similarly  precipitates  only  globulins,  if 
the  solution  is  neutral,  but  all  except  peptones,  if  acid  is  added. 

Metal  Albuminates.  —  Salts  of  certain  metals,  e.g.,  mercuric 
chloride,  HgCl2,  and  lead  acetate,  (CH3COO)2Pb.  precipitate  albumins 
from  solution  in  the  form  of  insoluble  metal  albuminates.  These 
reactions  are  the  basis  for  the  use  of  white  of  egg  as  an  antidote  for 
poisoning  with  mercuric  chloride. 

Precipitated  M  eta-proteins.  —  Mineral  acids,  nitric,  hydrochloric, 
sulphuric  and  strong  organic  acids,  like  acetic  acid,  precipitate  albumins 
as  insoluble  primary  derived  proteins,  meta-  proteins. 


PROTEINS  407 

Soluble  Acid  Albuminates. — These  meta-proteins  are  dissolved 
with  excess  of  acid  in  the  form  of  soluble  acid  albuminates. 

Heller's  Ring  Test. — The  precipitation  of  albumin  with  nitric  acid 
is  the  basis  for  an  important  clinical  test  for  albumin,  especially  in 
urine.  5  c.c.  of  urine  are  placed  in  a  test  tube,  or  conical  test  glass,  and 
an  equal  volume  of  strong  nitric  acid  is  added  at  the  bottom  by  means  of 
a  pipette.  At  the  zone  between  the  two  liquids  a  cloud  of  precipitated 
albumin  will  appear  on  standing  even  if  a  small  trace  is  present. 

Precipitated  Protein  Salts. — Other  acids,  e.g.,  picric,  phospho- 
tungstic  and  tannic  acids,  precipitate  albumins  from  solution  in  the 
form  of  insoluble  protein  salts.  The  alkali  salts  of  these  acids  cause  no 
precipitation.  These  precipitation  tests  are  used  in  salting  out  methods 
for  the  separation  of  the  proteins,  but  the  limits  of  differentiation 
are  not  sharp  and  much  care  is  needed  to  make  the  separations  valuable. 
More  specific  details  as  to  methods  of  manipulation  may  be  found  in 
laboratory  texts  on  physiological  chemistry. 


408  ORGANIC  CHEMISTRY 


XII.  CYANOGEN,  CYANIDES,  CYANATES 

In  our  discussion  -of  the  various  groups  of  compounds  we  have  re- 
peatedly referred  to  the  cyanogen  substitution  products  as  analogous 
to  the  halogen,  hydroxyl  and  amino  compounds,  e.g,  CH3  —  €1,  methyl 
chloride;  CH3—  OH,  methyl  (hydroxide)  alcohol;  CH3—  NH2,  methyl 
amine;  CH3  —  CN,  methyl  cyanide.  The  group  (  —  CN)  acts  in  all 
respects  as  a  monovalent  radical,  the  compounds  being  termed  cyanides 
or  cyano  compounds. 

A.  CYANOGEN  OR  DI-CYANOGEN 

The  cyanide  radical  is  one  of  the  examples  of  a  radical  existing  as 
such.  It  is  known  as  cyanogen  and  is  made  by  heating  mercuric  cya- 
nide just  as  oxygen  is  made  by  heating  mercuric  oxide. 

2HgO         —  >        O2  or  O  =  O  +  2Hg 

Mercuric  oxide  Oxygen 

Hg(CN)2         -  >         (CN)2  or  N  =  C—  C=N  +  Hg 

Mercuric  cyanide  Cyanogen 

It  may  also  be  formed  by  passing  nitrogen  over  an  electric  arc 
between  carbon  electrodes. 


c  +  N 

Cyanogen 

That  cyanogen  is  N  =  C  —  C^N  is  proven  both  by  its  analogy  to  mole- 
cular oxygen,  in  the  above  formation  from  mercuric  cyanide,  and  by 
the  fact  that  it  is  the  nitrite  of  oxalic  acid.  When  hydrolyzed  it  reacts 
with  four  molecules  of  water  and  yields  oxalic  acid  and  ammonia  which 
then,  of  course,  unite  and  form  ammonium  oxalate. 


HiOH      HOiH 

N  =  C— C  =  N +  4H2O      or      N  =  |C C  =  |N 

H2 


Cyanogen  iQ 


HO        OH  COONH4 


2NH3  —  >        COONH4 

Ammonium 
oxalate 


o      o 

Oxalic  acid 


CYANOGEN,   CYANIDES,    CYANATES,    ETC.  409 

The  reverse  of  this  reaction  also  occurs  and  ammonium  oxalate  yields 
cyanogen  by  the  loss  of  four  molecules  of  water,  oxamide  (p.  272)  being 
the  intermediate  product. 

COONH2H2       -2H20      CONH2     -2H2O      CN 

I  ">         I  I 

COONH2H2  CONH2  CN 

Ammonium  oxalate  Oxamide  Cyanogen 

This  is  exactly  analogous  to  the  relation  between  ammonium  acetate, 
acetamide  and  acetic  nitrile  or  methyl  cyanide  (p.  148).  As  cyanogen 
is  a  ^'-cyanide  or  a  ^'-nitrile  we  would  expect  an  intermediate  product 
formed  by  the  hydrolysis  of  only  one  nitrile  group.  Such  a  compound 
would  be  cyano  formic  acid  and  a  semi-nitrile  of  oxalic  acid. 

CN  CN 

+      2H2O  -*        |  +        NH3 

CN  COOH 

Cyanogen  Cyano  formic 

acid 

The  compound  is  not  known  free  but  in  the  form  of  its  esters. 

Cyanogen  is  a  stable  colorless  gas  with  a  sharp  odor.  It  is  easily 
condensed  to  a  colorless  liquid  boiling  at  —20.7°  and  solidifies,  when 
cooled  below  this  temperature,  to  crystals  which  melt  at  —34.4°. 
Gaseous  cyanogen  burns  with  a  blue  flame  and  is  decomposed  only  at 
high  temperatures  (above  800°).  It  is  soluble  in  water  but  the  water 
solution  is  unstable,  decomposing  into  oxalic  acid,  ammonia,  carbon 
dioxide,  hydrogen  cyanide  and  urea.  With  alkalies  cyanogen  yields 
cyanides  and  cyanates. 


(CN)2     +     KOH        -  >        KCN      +      KOCN      +      H2O 

Cyanogen  Potassium  Potassium 

cyanide  cyanate 

This  is  analogous  to  the  reaction  of  chlorine  and  alkalies. 

C12      +      KOH        -  --  >        KC1      -|-      KOC1      +      H20 

Chlorine  Potassium  Potassium 

chloride  hypochlorite 

B.  HYDROCYANIC  ACID  AND  ITS  SALTS 
Hydrocyanic  Acid  H  —  CN  Hydrogen  Cyanide 

Hydrocyanic  acid  or  hydrogen  cyanide  is  the  simple  binary  acid  of 
cyanogen,  corresponding  to  hydrochloric  acid,  the  binary  acid  of  chlorine. 

' 


410  ORGANIC  CHEMISTRY 

The  group  (CN)  is  considered  as  a  unit  and  is  sometimes  denoted  by 
the  symbol  Cy,  but  this  is  not  desirable. 

(CN)2  H— (CN) 

Cyanogen  Hydrocyanic  acid 

C12  H— Cl 

Chlorine  Hydrochloric  acid 

Hydrocyanic  acid  is  most  easily  prepared  from  its  potassium  salt, 
K(CN),  which  is  obtained  principally  by  the  decomposition  of  the 
complex  double  cyanides  of  iron  as  we  shall  soon  consider.  The  acid 
is  also  obtained  by  the  hydrolysis  of  certain  glucosides,  e.g.,  amygdalin, 
in  bitter  almonds.  It  is  prepared  synthetically  by  reactions  to  be 
discussed  presently  in  connection  with  the  constitution  of  it  and  its 
salts.  It  is  a  colorless  liquid  with  a  characteristic  odor  and  burns  with 
a  violet  flame.  It  boils  at  26.1°  and  solidifies  to  crystals  which  melt 
at  —14°.  It  is  an  extremely  strong  poison,  the  best  antidotes  being 
chlorine  and  hydrogen  dioxide.  It  is  readily  absorbed  by  metallic 
nickel  which  is  thus  used  in  gas  masks  for  this  purpose.  It  is  stable  in 
dry  air  but  in  presence  of  water  is  readily  hydrolyzed  yielding  ammonia 
and  formic  acid  as  the  chief  products. 

H— CN    +     2H2O      >      H— COOH    +    NH3 

Hydrocyanic  Formic  acid 

acid 

Formic  Nitrile. — It  is  thus  known  also  as  formic  nitrile. 

Metal  Cyanides 

The  two  simple  salts  of  hydrocyanic  acid  which  are  used  in  the 
synthesis  of  organic  cyanogen  compounds  are  potassium  cyanide, 
K — (CN),  and  silver  cyanide,  Ag — (CN).  These  are  both  prepared 
by  the  action  of  the  metallic  oxides  or  hydroxides  on  the  acid. 

H— (CN)      +      KOH          >      .  K— (CN)       +      H2O 

Hydrocyanic  acid  Potassium  cyanide 

H— (CN)      +      AgOH        >        Ag— (CN)      +      H2O 

Silver  cyanide 

The  silver  cyanide  is  also  formed  by  the  reaction  between  potassium 
cyanide  and  silver  nitrate. 

K— (CN)      +      AgN03        >        Ag— (CN)      +      KNO3 

Potassium  cyanide  Silver  cyanide 


CYANOGEN,    CYANIDES,    CYANATES,    ETC.  411 

Potassium  cyanide  is  a  white  deliquescent  solid  readily  soluble  in 
water.  It  is  easily  decomposed  by  boiling  the  water  solution  and  yields 
potassium  formate  and  ammonia.  Like  hydrocyanic  acid  it  is  an 
extremely  violent  poison,  probably  due  to  its  hydrolysis  into  the  free  acid. 
It  also  yields  hydrocyanic  acid  by  the  action  of  carbonic  acid. 
It  is  prepared  commercially  by  the  decomposition  of  the  double  cy- 
anide of  iron  and  potassium,  potassium  ferro-cyanide,  K4Fe(CN)6. 
In  recent  years  it  has  been  used  extensively  as  a  solvent  for  gold  in  the 
recovery  of  this  metal  from  low-yielding  ores. 

Silver  cyanide  is  a  white  solid  readily  formed  as  a  precipitate  when 
solutions  of  silver  are  treated  with  potassium  cyanide.  It  is  readily 
soluble  in  excess  of  potassium  cyanide  forming  the  double  cyanide  of 
silver  and  potassium.  It  is  also  soluble  in  ammonium  hydroxide. 

K— (CN)  +  AgNO3     >    Ag— (CN)  +  KNO3 

Potassium  Silver  cyanide 

cyanide  (in&ol.) 

Ag— (CN)  +  K— CN       — >    KAg(CN)2  or  KCN.AgCN 

Silver  cyanide  Potassium  silver 

cyanide  (soluble) 

Constitution. — The  problem  of  the  constitution  of  hydrocyanic  acid 
and  its  simple  salts  potassium  cyanide  and  silver  cyanide  is  a  very 
interesting  one  though  the  facts  bearing  upon  it  are  very  puzzling. 
In  considering  the  cyanogen  substitution  products  of  the  hydrocarbons 
we  showed  by  very  satisfactory  evidence  that  they  existed  in  two  dis- 
tinct isomeric  forms,  viz.,  alkyl  cyanides,  R — C  =  N  and  alkyl  iso- 
cyanides  R — N  =  C  or  R — N  =  C.  The  proofs  for  this  view  are  fur- 
nished by  the  hydrolytic  decomposition  of  the  two  compounds  (p.  69). 
The  products  obtained  show  conclusively  that  in  the  cyanides  the 
alkyl  carbon  atom  is  linked  to  the  carbon  atom  of  the  cyanogen  radical, 
while  in  the  iso-cyanides ,  the  alkyl  carbon  atom  is  linked  to  the  nitrogen 
atom  of  the  cyanogen. 

H)— OH 
CH3— C  =  (N  +  H)\  — >     CH3— COOH  +  NH3 

Methyl  cyanide  TT\  /  U  Acetic  acid 

Acetic  nitrile  **>)' 

CH3— N  =  C    +    2H2O >        CH3— NH2    +    H— COOH 

Methyl  iso-cyanide  Methyl  amine  Formic  acid 

Now  while  isomerism  exists  in  the  alkyl  cyanogen  compounds  there  is 
no  isomerism  in  the  case  of  either  hydrocyanic  acid,  potassium  cyanide 
or  silver  cyanide.  Each  of  these  compounds  is  known  in  only  one  form. 


412  ORGANIC  CHEMISTRY 

It  would  seem  therefore  that  the  only  problem  would  be  to  determine 
whether  they  exist  in  the  form  of  alkyl  cyanides,  i.e.,  with  the  hydrogen, 
potassium  or  silver  linked  to  the  carbon  atom  of  the  cyanogen  or 
whether  they  are  in  the  form  of  the  alkyl  isocyanides  with  the  nitrogen 
atom  of  the  cyanogen  group  linked  to  the  other  element.  This,  however, 
is  where  the  facts  become  perplexing. 

Synthesis  from  Cyanogen. — Two  methods  of  synthesis  of  hydro- 
cyanic acid  support  the  view  that  this  compound  has  the  cyanide  struc- 
ture and  not  the  iso-cyanide.  Cyanogen  gas  because  it  yields  oxalic 
acid  on  hydrolysis  must  have  the  constitution  in  which  the  two  cyano- 
gen groups  are  linked  by  the  carbon  atoms  rather  than  nitrogen. 

C  =  N        2H20  COOH 

|  +  ->         |  +    ?NH3 

C^N        2H2O  COOH 

Cyanogen  Oxalic  acid 

Now  cyanogen  yields  hydrocyanic  acid  when  acted  upon  by  hydrogen 
under  the  influence  of  a  silent  electrical  discharge.  The  only  way  for 
hydrogen  to  split  the  cyanogen  molecule  and  form  hydrocyanic  acid 
would  be  at  the  union  between  the  two  carbon  atoms.  The  hydrogen 
itself  thus  becoming  linked  to  carbon 

N^C C  =  N  +  H2        >        N^C— H    +    H— C  =  N 

Cyanogen  Hydrocyanic  acid 

From  Acetylene. — The  second  synthesis  of  hydrocyanic  acid  sup- 
porting this  same  constitution  is  from  acetylene  by  reaction  with  nitro- 
gen under  the  influence  of  an  electrical  discharge.  The  nitrogen  would 
split  the  acetylene  molecule  at  the  triple  linkage  of  the  two  carbons 
leaving  each  hydrogen  linked  to  carbon  in  the  hydrocyanic  acid. 

H— C  =  C— H  +  N2        — »        H— C  =  N  +  N  =  C— H 

Acetylene  Hydrocyanic  acid 

From  Ammonia. — A  third  method  for  the  synthesis  of  hydrocyanic 
acid  supports  the  constitution  of  an  iso-cyanide  with  the  linkage  of 
hydrogen  to  nitrogen.  The  Hofmann  iso-nitrile  reaction  (p.  71) 
consists  in  the  formation  of  iso-cyanides  (iso-nitriles)  by  the  reaction 
between  chloroform  and  primary  amines  in  the  presence  of  an  alkali. 

-3HC1 
R— N(H2)  +  C(HCla).  (+KOH)  R— N  =  C 

Primary  amine  Iso-cyanide 


CYANOGEN,   CYANIDES,   CYANATES,   ETC.  413 

Now  if  instead  of  a  primary  amine  we  use  ammonia  the  product  is 
hydrocyanic  acid. 

-3HC1 
H— N(H2)  +  C(HCls)  (+KOH)  H— N=C      or      H— C  =  N 

Ammonia  Hydrocyanic  acid 

Alkyl  Cyanides  from  Potassium  Cyanide. — That  potassium  cyanide 
has  the  constitution  corresponding  to  an  alkyl  cyanide  is  supported  by 
the  fact  that  alkyl  halides  with  potassium  cyanide  yield  alkyl  cyanides 
and  not  isocyanides. 

R— I     +     K— C  =  N        >        R— C  =  N     +     KI 

Alkyl  halide*  Alkyl  cyanide 

Alkyl  Iso-cyanides  from  Silver  Cyanide. — On  the  other  hand  silver 
cyanide  would  seem  to  have  the  constitution  of  an  iso-cyanide  because  it 
yields  alkyl  iso-cyanides  with  alkyl  halides. 

R— I     +     Ag— N  =  C        >        R— N  =  C     +     Agl 

Alkyl  halide  Alkyl  iso-cyanide 

While  these  reactions  support  one  constitution  for  potassium  cyanide 
and  the  other  for  silver  cyanide  yet  the  two  compounds  are  each  pre- 
pared from  hydrocyanic  acid  by  the  action  of  the  respective  metallic 
hydroxides. 

H— C^N     +     KOH        >        K— C  =  N     +     H2O 

Hydrocyanic  acid  Potassium  cyanide 

(as  a  cyanide) 

H— N  =  C     +     AgOH  — »        Ag— N  =  C     +     H2O 

Hydrocyanic  acid  Silver  cyanide 

(as  an  iso-cyanide) 

Also,  which  is  still  more  perplexing,  the  potassium  cyanide,  which 
seems  to  have  the  constitution  of  a  cyanide  when  it  reacts  with  silver 
nitrate  yields  silver  cyanide  which,  as  above,  seems  to  have  the  con- 
stitution of  an  isocyanide. 

K— C  =  N      +      AgNO3        >        Ag— N  =  C      +      KNO8 

Potassium  cyanide  Silver  cyanide 

(cyanide  structure)  (iso-cyanide  structure) 

Tautomerism. — While  therefore  these  three  cyanogen  compounds 
do  not  exist  in  isomeric  forms  as  do  the  alkyl  cyanogen  compounds  yet 
we  cannot  assign  one  definite  formula  to  each  compound  because  the 
evidence  goes  to  show  that  sometimes  one  formula  and  sometimes  the 
other  is  the  true  representation  of  the  constitution.  The  two  forms  probably 
exist  together  in  equilibrium  the  conditions  of  which  are  different  for 
each  of  the  compounds  so  that  though  they  are  very  similar  in  character 
their  apparent  constitution  is  different.  Thus  we  have  another  inter- 


414  ORGANIC  CHEMISTRY 

esting  case  of  the  peculiar  phenomenon  of  tautomerism  as  was  found 
especially  in  the  case  of  aceto-acetic  ester  (p.  256).  In  writing  the 
formulas  therefore  it  is  best  not  to  indicate  a  definite  constitution  but 
simply  the  linkage  o^f  the  cyanogen  group  as  a  whole  with  the  other 
elements. 

H—  (CN)  K—  (CN)  Ag—  (CN) 

Hydrocyanic  acid  Potassium  cyanide  Silver  cyanide 

Complex  Iron-cyanide  Compounds 

Aside  from  potassium  cyanide  in  its  use  for  the  extraction  of  gold 
the  most  important  cyanides  commercially  are  the  double  cyanides  of 
iron  and  potassium. 

Ferrous  and  Ferric  Cyanides.  —  Iron  being  both  bivalent  and  triva- 
lent  forms  two  salts  with  hydrocyanic  acid 

Fe"(CN)2  Fe'"(CN)3 

Ferrous  cyanide  Ferric  cyanide 

These  two  simple  salts  are  not  known  ;  but  with  hydrocyanic  acid,  with 
potassium  cyanide,  with  themselves  or  with  each  other,  they  form  well 
known  double  cyanides.  These  double  cyanides,  however,  are  really 
simple  compounds  which  dissociate,  in  solution,  into  two  ions,  viz., 
the  cation,  of  hydrogen  or  the  metal,  and  a  complex  anion,  consisting 
of  iron  and  the  cyanogen  group. 

Hydro-ferrocyanic  and  Hydro-ferricyanic  Acids.  —  The  acids  which 
are  the  mother  substances  of  these  complex  cyanides  may  be  obtained 
from  the  potassium  salts  by  treating  with  strong  acids.  They  are: 


H4    (Fe"(CN),)~  H3    (Fe'"(CN)6) 

Hydro-ferro-cyanic  acid  Hydro-ferri-cyanic  acid 

Potassium  Salts.  —  These  two  acids  form  salts  with  potassium  as 
follows  : 

4(4-)  3(+) 

K4    (Fe"(CN),)~  K3    (Fe'"(CN)«) 

Potassium  ferro-cyanide  Potassium  ferri-cyanide 

Iron  Salts.  —  They  also  form  salts  with  iron  both  as  ous  salts  and  as 
ic  salts. 


e2"    (Fe"(CN)6)~  Fe,"    (Fe"'(CN)6)2 

Ferrous  ferro-cyanide  Ferrous  ferri-cyanide 


Fe/"     (Fe"(CN)6)3  Fe"'    (Fe"'(CN)6) 

Ferric  ferro-cyanide  Ferric  ferri-cyanide 


CYANOGEN,    CYANIDES,    CYANATES,    ETC.  415 

In  all  of  these  ferro-  and  f  erri-cyanides  we  have  the  complex  anions 
(Fe"(CN)6),s  ferro  -cyanide,  and  (Fe"'(CN)6),s  fern-cyanide.  The 
ferro-cyanide  ion  possesses  four  negative  charges  and  the  iron  is  in  the 
ous  condition;  while  the  ferri-cyanide  ion  possesses  three  negative  charges 
and  the  iron  is  in  the  ic  condition.  In  order  to  indicate  their  double 
salt  composition  these  formulas  are  sometimes  written  as  follows, 
illustrating  with  the  potassium  salts. 


K4    (Fe"(CN)6)~          or        4KCN.Fe(CN)2 

Potassium  ferro- 
cyanide 

K3    (Fe'"(CN)6)  or  3KCN.Fe'"(CN)3 

Potassium  ferri-cyanide 

While  these  formulas  express  the  double  salt  composition  they  do  not 
indicate  how  the  compounds  dissociate  in  solution  and  how  solutions 
of  them  react. 

The  iron  salts  of  ferro  and  ferricyanic  acid  are  the  compounds  to 
which  the  names  cyanogen  and  cyanide  are  due.  Two  of  these  salts 
are  of  deep  blue  color  and  the  Greek  word  from  which  cyanogen  and 
cyanide  are  derived  is  cyanos  which  means  blue.  The  ferric  ferro-cya- 
nide, Fe4"'(Fe"(CN6)3,  is  known  as  Prussian  blue  and  the  ferrous  ferri- 
cyanide,  Fe3"(Fe'"(CN)6)2,  is  Turnbull's  blue.  These  compounds  are 
formed  when  ferric  salts  in  solution  are  treated  with  potassium  ferro- 
cyanide  and  when  ferrous  salts  in  solution  are  treated  with  potassium 
ferricyanide/  They  are  common  qualitative  tests  for  the  two  forms  of  ( 
iron  salts.  The  compounds  are  also  used  as  laundry  blueing  and  are 
formed  in  the  blue  print  process  of  photography. 

Potassium  Ferro-cyanide.  —  Potassium  ferro-cyanide  is  commer- 
cially prepared  by  heating  nitrogenous  organic  material,  i.e.,  protein 
(blood,  hair,  horn,  leather,  etc.)  with  potassium  carbonate  and  iron 
filings.  The  mixture  is  heated  red  hot,  after  cooling  is  extracted 
with  water  and  the  potassium  ferro-cyanide  crystallized  out. 
Protein  +  K2CO3  +  Fe  -  >  K4Fe.(CN)6 

Potassium  ferro-cyanide 

Potassium  ferro-cyanide  so  prepared  is  the  starting  point  for  the 
preparation  of  the  other  cyanogen  compounds.     When  distilled  with 
dilute  sulphuric  acid,  hydrogen  cyanide  is  evolved. 
2K4Fe(CN)6  +  3H2S04        --  >        6HCN  +  K2Fe2(CN)6  +  3K2SO4 

Potassium  Hydrogen 

ferro-cyanide  cyanide 


41 6  ORGANIC  CHEMISTRY 

When  heated  alone  it  decomposes  yielding  potassium  cyanide,  iron 
carbide  and  nitrogen. 

K4Fe(CN)6 >        4KCN  +  FeC2  +  N2 

Potassium  ferro-  Potassium 

cyanide  cyanide 

When  similarly  heated  with  potassium  carbonate  a  larger  yield  of  potas- 
sium cyanide  is  obtained. 

K4Fe(CN)6  +   K2CO3 >       5KCN   +   KOCN   +   CO2   +   Fe 

Potassium  Potassium          Potassium 

ferro-cyanide  cyanide  cyanate 

Heated  with  metallic  sodium  all  of  the  cyanogen  is  obtained  as  cyanide. 

K4Fe(CN)6  +   2Na       — »       4KCN  +   2NaCN  +   Fe 

Potassium  Potassium  Sodium 

ferro-cyanide  cyanide  cyanide 

On  oxidation  of  the  ferro-cyanide  by  means  of  potassium  permanganate, 
potassium  bichromate,  bromine  or  chlorine,  the  ferri-cyanide  is  ob- 
tained. 

2K4Fe(CN)6    +    0  — >        2K3Fe(CN)6    +    K2O 

K4Fe(CN)6    +    Cl  K3Fe(CN)6    +    KC1 

Potassium  ferro-  Potassium  ferri- 

cyanide  cyanide 

C.  CYANIC  ACID,  ISO-CYANIC  ACID,  THIO-CYANIC  ACID 
AND  THEIR  SALTS 

Cyanic  and  Iso -cyanic  Acids  and  Salts 

Iso-cyanic  Acid. — If  hydrocyanic  acid  is  analogous  to  hydrochloric 
acid  we  should  expect  an  oxygen  acid  to  be  obtained  from  it  analogous 
to  hypochlorous  acid. 

HC1  HOC1 

Hydrov   loric  acid  Hypochlorous  acid 

HCN  HOCN 

Hydrocyanic  acid  Cyanic  acid 

An  acid  of  this  composition  is  known  but  it  has  been  shown  to  have 
another  constitution,  viz.,  H — N  =  C  =  O,  and  is  iso-cyanic  acid  though 
it  is  often  called  cyanic  acid.  It  is  an  odorous,  unstable  liquid.  We 
have  already  discussed  (p.  73)  the  alkyl  derivatives  of  these  two  acids. 

R— O— C^N  R— N  =  C  =  0 

Alkyl  cyanates  Alkyl  iso-cyanates 


CYANOGEN,    CYANIDES,    CYANATES,    ETC.  417 

Thus  while  isomeric  derivatives  are  known  corresponding  to  two 
isomeric  acids  only  one  acid  is  known  and  this  one  has  the  structure  of 
the  iso-cyanic  acid.  When  we  study  the  salts  obtained  from  this  iso- 
cyanic  acid  we  find,  unlike  the  alkyl  derivatives,  that  they  are  known 
in  only  one  form  but  strangely  enough  in  the  form  of  the  cyanic  acid, 
e.g.,  K  —  O  —  C  =  N,  potassium  cyanate. 

Potassium  Cyanate.—  When  iso-cyanic  acid  is  neutralized  with 
potassium  hydroxide,  potassium  cyanate  is  obtained.  Potassium 
cyanate  is  also  obtained  when  potassium  cyanide  is  oxidized  by 
means  of  lead  oxide  or  potassium  bichromate. 


H—  N  =  C  =  O     +     KOH        --  > 

Iso-cyanic  acid  Potassium  cyanate 

KCN       +        O  -  >  KOCN 

Potassium  cyanide  Potassium  cyanate 

The  preparation  of  this  compound  by  this  reaction  is  an  exceedingly 
striking  one.  It  is  usually  accomplished  by  heating  anhydrous  potas- 
sium ferro-cyanide  with  dry  potassium  bichromate  in  an  iron  dish. 
The  ferro-cyanide  is  first  decomposed  by  the  heat  as  previously 
described  (p.  416)  yielding  five  molecules  of  potassium  cyanide  and  one 
molecule  of  potassium  cyanate.  The  potassium  cyanide  is  then  oxi- 
dized by  the  bichromate  to  potassium  cyanate.  A  little  of  the  mixed 
ferro-cyanide  and  bichromate  is  placed  in  the  center  of  a  hot  iron  dish. 
The  mass  soon  glows  and  becomes  red  hot  at  the  same  time  turning 
black  due  to  the  setting  free  of  the  iron.  A  tinge  of  green  is  also  often 
observed  indicating  reduction  of  the  bichromate.  The  outside  heat 
may  now  be  removed  and  as  fresh  mixture  is  added,  in  small  quantities 
at  a  time,  the  reaction  continues  until  a  black  mound  is  formed  which 
is  red  hot  all  through.  This  is  then  cooled,  extracted  with  hot  alcohol 
and  filtered  into  a  cold  dish  when  the  potassium  cyanate  separates  out 
in  fine  crystals.  Potassium  cyanate  bears  the  same  relation  to  potas- 
sium cyanide  that  potassium  hypochlorite  bears  to  potassium  chloride. 
They  are  respectively  formed  when  chlorine  gas  or  cyanogen  gas  is 
passed  into  potassium  hydroxide. 

C12      +      KOH        -  >        KC1      -f      KOC1 

Chlorine  Potassium  Potassium 

chloride  hypochlorite 

(CN)2      +      KOH        -  >        KCN      +      KOCN 

Cyanogen  Potassium  Potassium 

cyanide  cyanate 

27 


41 8  ORGANIC  CHEMISTRY 

Ammonium  Cyanate. — The  corresponding  ammonium  salt,  viz., 
ammonium  cyanate,  NH4OCN,  may  be  easily  prepared  from  the  potas- 
sium cyanate  by  treating  a  solution  of  the  latter  with  the  calculated 
amount  of  ammonium  sulphate.  This  compound  is  of  especial  interest 
because  on  evaporation  of  the  water  solution  to  dryness  a  rearrange- 
ment takes  place  and  urea  is  formed  (p.  429).  Ammonium  cyanate 
is  also  formed  when  iso-cyanic  acid  is  neutralized  with  ammonia. 

H— N  =  C  =  0     +     NH4OH    >    NH4— O— C  =  N 

Iso-cyanic  acid  Ammonium  cyanate 

Such  a  rearrangement  when  iso-cyanic  acid  is  neutralized  and  converted 
into  salts  of  cyanic*  acid  is  an  interesting  phenomenon. 

Cyanuric  Acid. — That  iso-cyanic  acid  has  the  constitution  given  to 
it  is  established  by  the  constitution  of  the  alkyl  derivatives  which 
are  not  true  esters  (p.  73)  and  also  by  its  relation  to  cyanuric  acid. 
This  latter  acid  is  a  polymer  of  iso-cyanic  acid,  viz.,  (HNCO)3.  It  is 
obtained  by  heating  urea  and  the  reactions  will  be  considered  presently 
when  we  study  this  compound.  This  source  of  the  acid  is  the  basis  of 
the  name  cyan-uric  acid.  It  is  a  solid  crystallizing  from  water  solution 
in  prisms  which  contain  two  molecules  of  water  of  crystalliza- 
tion. Like  iso-cyanic  acid  cyanuric  acid  yields  alkyl  derivatives  of 
two  isomeric  forms,  corresponding  to  polymers  of  cyanic  and  iso-cya- 
nic acid  derivatives.  The  ethyl  derivatives  have  the  following 
constitutions : 

OC2H5  O 


N      N  H5C2— N       N— C2H5 

II        I  I         I 

H5C2O--C      C— OC2H5  O  =  C       C  =  O 


N  N 

Ethyl  cyanurate 

C2H5 

Ethyl  iso-cyanurate 

In  all  of  these  cyanogen  compounds  we  have  this  striking  phenom- 
enon of  the  probable  existence  of  tautomeric  forms  in  equilibrium.  In 
some  cases,  as  in  the  acids  and  the  metal  salts,  the  conditions  of  equi- 


CYANOGEN,    CYANIDES,    CYANATES,    ETC.  419 

librium  are  such  that  only  one  form  is  known  which,  however,  yields 
derivatives  of  the  other  form.  In  other  cases,  as  in  the  alkyl  derivatives, 
the  conditions  of  equilibrium  are  such  that  both  forms  are  known. 

Fulminic  Acid. — Detonating  caps  used  for  exploding  the  charges  of 
gun  cartridges,  shells  and  dynamite  cartridges  are  made  of  mercury 
fulminate,  a  salt  of  fulminic  acid.  This  acid  has  the  same  composition 
as  cyanic  acid  and  iso-cyanic  acid.  The  constitution  is,  however, 
different  from  either  and  is  that  of  a  normal  iso-cyanic  acid  in  which  the 
hydrogen  is  linked,  as  hydroxyl,  to  the  nitrogen  and  not  directly  as  in 
iso-cyanic  acid. 

H— O— C  =  N    H— N=C  =  O     H— O— N=CorH— O— N  =  C 

Cyanic  acid  Iso-cyanic  acid  Fulminic  acid 

This  constitution  is  established  by  the  hydrolysis  of  the  acid  by 
means  of  concentrated  hydrochloric  acid.  In  this  reaction  which  takes 
place  in  two  steps  the  hydrochloric  acid  is  first  added  directly  to  the 
compound  forming  an  intermediate  product  and  this  then  hydrolyzes, 
yielding  hydroxyl  amine  and  formic  acid 

HO— N  =  C     H-     HC1 >HO— N  =  C— Cl 

Fulminic  acid 

H 

Oxime  of  formyl  chloride 

HO— N  =  I  =  C—  (Cl+H)— OH > 

+     H2!O  H 

Oxime  +  2  Water 

HO— NH2     +         O=C— OH        +     HC1 
H 

Hydroxyl  amine  Formic  acid 

Bivalent  Carbon. — This  reaction  supports  the  constitution  as  given 
and  the  view  that  in  this  compound  we  have  a  bivalent  carbon  atom-. 

Mercuric  Fulminate.— The  mercury  and  silver  salts  of  fulminic  acid 
are  both  detonating  explosives  the  former  being  the  one  used  in  detonat- 
ing caps. 

Hg(ONC)2  AgONC 

Mercuric  fulminate  Silver  fulminate 

Mercuric  fulminate  is  prepared  by  the  action  of  nitric  acid  on  mercury 
and  the  subsequent  action  of  ethyl  alcohol.  The  fulminate  settles  out 
as  a  white  powder  which  is  very  explosive  when  dry  but  may  be  safely 


420  ORGANIC  CHEMISTRY 

handled  in  the  moist  condition.  The  fulminate  detonating  caps  may 
be  exploded  by  percussion  as  in  the  case  of  gun  cartridges  or  by  means 
of  heat  produced  by  a  burning  fuse  or  by  an  electric  spark  as  in  the  case 
of  shells  and  dynamite  cartridges. 

Thio-cyanic  Acid  and  Salts 

Corresponding  to  the  cyanic  and  iso-cyanic  acids  and  their  salts 
and  esters,  we  have  the  analogous  sulphur  or  thio  compounds  formed  by 
the  replacement  of  oxygen  by  sulphur.  The  relationship  of  these 
sulphur  compounds  to  the  oxygen  compounds  is  exactly  the  same  as 
that  existing  between  sulphuric  acid  and  thio-sulphuric  acid. 

HO— SO2— OH  HO— SO2— SH 

Sulphuric  acid  Thio-sulphuric  acid 

HO— C  =  N  HS— C  =  N 

Cyanic  acid  Thio-cyanic  acid 

While  free  cyanic  acid  is  not  known  the  thio-cyanic  acid  is  a  more  or 
less  stable  liquid.  The  salts  of  thio-cyanic  acid  are  also  known,  two  of 
them  being  quite  common  reagents,  viz., 

KSCN  NH4SCN 

Potassium  Ammonium 

thio-cyanate  thio-cyanate 

With  ferric  salts  in  solution  either  of  these  reagents  forms  the  cherry 
red  ferric  thio-cyanate  and  is  the  basis  of  qualitative  tests  for  iron  and 
the  use  of  the  thio-cyanate  as  an  indicator  in  volumetric  titrations. 
Potassium  thio-cyanate  may  be  prepared  by  heating  potassium  cyanide 
with  sulphur  or  ammonium  sulphide.  Ammonium  thio-cyanate  may 
be  prepared  by  heating  together  carbon  disulphide  and  ammonia  in 
the  presence  of  alcohol. 

KCN      +      S        >        KSCN 

Potassium  Potassium  thio- 

cyanide  cyanate 

CS2      +      2NH.3        >        NH4S— C  =  N      +      H2S 

Ammonium 
thio-cyanate 

This  compound  undergoes  rearrangement  the  same  as  ammonium 
cyanate  and  thio-urea  is  obtained.  With  a  soluble  mercuric  salt  am- 
monium thiocyanate  precipitates  mercuric  thio-cyanate  which  on  heat- 
ing swells  up  into  phantastic  shapes  which  are  known  as  Pharaoh* s 
serpents.  The  alkyl  thio-cyanates  are  known  and  have  been  discussed 
(p.  74).  Ally  1- thio-cyanate  is  a  constituent  of  oil  of  garlic.  These 


CYANOGEN,   CYANIDES,   CYANATES,   ETC.  421 

compounds  are  true  sulphur  esters  agreeing  with  the  constitution  of 
thio-cyanic  acid  as  HSCN. 

Iso-thio-cyanates. — Isomeric  with  the  thio-cyanic  acid  would  be 
iso -thio-cyanic  acid  which  if  analogous  in  constitution  to  the  iso-cyanic 
acid  should  have  the  constitution  H — N  =  C  =  S.  Neither  this  com- 
pound nor  metal  salts  of  it  are  known  but  alkyl  derivatives  are  known  as 
constituents  of  oil  of  mustard  (p.  165). 

H2C  =  CH— CH2— N  =  C  =  S 

Allyl  iso-thio-cyanate 
Oil  of.  Mustard 

These  iso  compounds  are  obtained  from  the  thio-cyanates  by  heat  and 
their  constitution  is  analogous  to  that  of  the  alkyl  iso-cyanates.  They 
are  not  true  sulphur  esters  but  the  alkyl  radical  is  linked  to  nitrogen 
as  is  proven  by  their  hydrolysis  to  primary  amines. 

Cyanogen  Chloride  and  Cyan-amide 

Cyanogen  Chloride. — This  compound  is  the  simple  chlorine  com- 
pound of  cyanogen  and  is  formed  by  the  action  of  chlorine  on  hydro- 
cyanic acid. 

HCN      +      C12        >        Cl— CN      +      HC1 

Hydrocyanic  Cyanogen 

acid  chloride 

It  is  a  soluble  colorless  gas  with  a  strong  odor  and  is  used  in  synthe- 
sizing cyanogen  compounds. 

Cl— CN      +      2KOH        >        KOCN     +      KC1      +      H2O 

Cyanogen  Potassium 

chloride  cyanate 

Cl— CN     +      C2H5ONa  -»        C2H5OCN     +      NaCl 

Cyanogen  Sodium  Ethyl  cyanate 

chloride  ethylate 

Cyanamide. — An  important  compound  formed  from  cyanogen  chlo- 
ride is  known  as  cyan-amide  and  as  its  name  indicates  is  composed  of 
the  cyanogen  radical  linked  to  the  amine  radical.     It  may  be  formed 
by  the  action  of  ammonia)  in  ethereal  solution,  on  cyanogen  chloride. 
Cl— CN      +      2NH3        >        NH2— CN     +      NH4C1 

Cyanogen  .          Cyan-amide 

chloride 

It  is  a  white  crystalline  substance  slightly  soluble  in  water.  This  com- 
pound is  of  especial  interest  because  it  acts  both  as  a  weak  base  and  as  a 
weak  acid.  The  metallic  salts  are  the  more  stable  and  the  most  im- 
portant one  is  the  calcium  salt. 


422  ORGANIC  CHEMISTRY 

Calcium  Cyanamide.— Calcium  cyan -amide  may  be  formed  from 
the  cyanamide  itself  by  the  action  of  lime. 

H2N— CN      +      Ca(OH)2        >        Ca  =  N— C  =  N      +      2H2O 

Cyan-amide  Calcium  cyan-amide 

This  synthesis,  however,  is  not  the  most  important  nor  the  most 
interesting. 

Fixation  of  Atmospheric  Nitrogen. — The  great  value  of  this  cyano- 
gen compound  lies  in  the  two  facts;  (i)  that  it  may  be  obtained  as  the 
result  of  the  fixation  of  atmospheric  nitrogen  and  (2)  that  it  is  a  valuable 
nitrogen  fertilizer. 

In  1895-1898  Caro  and  Frank  and  others  endeavored  to  synthesize 
cyanide  compounds  by  the  action  of  atmospheric  nitrogen  on  barium 
carbide  at  about  7OO°C.  They  obtained  only  small  yields  of  the  simple 
barium  cyanide,  but  much  larger  of  barium  cyan-amide.  In  utilizing 
calcium  carbide,  instead  of  barium  carbide,  a  yield  of  about  90  per  cent, 
of  the  cyan-amide  was  obtained  at  iooo°C.  The  preparation  of  the 
calcium  carbide  and  the  fixation  of  the  atmospheric  nitrogen  was  car- 
ried out  in  the  same  operation  by  heating  together  quick  lime,  CaO, 
carbon  arid  atmospheric  nitrogen  in  an  electric  furnace. 

CaO      +      C2      +      N2        — -»        Ca  =  N— C  =  N      +      CO 

Calcium  cyan-amide 

The  atmospheric  nitrogen  must  be  free  of  oxygen,  which  is  usually 
accomplished  by  passing  the  air  over  heated  copper,  or  by  utilizing 
nitrogen  obtained  from  liquid  air.  The  calcium  cyanamide  obtained 
contains  about  20  per  cent,  nitrogen. 

A  Source  of  Cyanides  and  Ammonia. — It  may  be  used  for  making 
potassium  or  sodium  cyanides  by  fusing  with  potassium  hydroxide  or 
sodium  hydroxide.  It  may  also  yieJd  ammonia  by  the  action  of  steam 
and  carbon  dioxide,  the  reaction  being  the  same  as  in  the  hydrolysis 
below. 

Fertilizer. — The  chief  interest  in  the  compound  is,  however,  in  its 
use  as  a  nitrogen  fertilizer,  for  which  purpose* about  50,0x30  tons  are 
made  annually,  at  the  present  time,  in  the  United  States.  The  manu- 
facture in  this  country  began  about  1909.  As  a  fertilizer  it  may  be 
used  either  directly  or  indirectly.  The  indirect  use  is  as  a  source  of 
ammonia,  by  the  method  just  referred  to.  The  ammonia  so  obtained 
is  then  converted  into  salts  which  are  the  actual  constituents  of  the 


CYANOGEN,    CYANIDES,    CYANATES,    ETC.  423 

fertilizers.  A  special  product  so  made  is  known  as  ammo-phos  and  con- 
tains both  ammonia-nitrogen  and  phosphoric  acid.  The  direct  use  is 
as  a  constituent  of  mixed  fertilizers,  in  which  case  it  is  usually  one  of 
several  nitrogen  compounds  present.  It  is  claimed  that,  in  general, 
the  crude  calcium  cyanamide  yields  its  nitrogen  to  crops  equally  with 
ammonium  sulphate  and  equal  to  90  per  cent  of  that  in  sodium  ni- 
trate. The  hydrolysis  of  the  compound  may  be  represented  by  the 
following  reaction. 

Ca  =  N—  C  =  N     +      3H2O        >        2NH3     +     CaO     +     CO2 

Calcium  cyan-amide 

The  decomposition  in  the  soil  is  however  influenced  by  varying  con- 
ditions and  by  the  presence  of  lime  and  other  fertilizer  salts  so  that 
its  exact  value  is  yet  in  question.  Among  the  products  obtained  by 
its  decomposition  in  the  soil  are;  ammonia  NH3,  calcium  carbonate, 
CaCO3,  cyan-amide,  H2N— CN,  di-cyan  di-amide,  (H2NCN)2  or 
H2N— (HN)C— NH(CN),  cyano  guanidine  and  urea  OC(NH2)2). 
Further  discusion  of  its  use  as  a  fertilizer  is  not  desirable  here. 

Sodium  Cyanide  from  Atmospheric  Nitrogen. — One  other  method 
for  the  fixation  of  atmospheric  nitrogen  in  the  form  of  cyanide  compounds 
should  be  mentioned  before  we  leave  the  subject  of  cyanogen  com- 
pounds. This  is  the  recent  American  process  of  Bucher  in  1917.  It 
consists  in  fixing  the  nitrogen  of  the  atmosphere  in  the  form  of  sodium 
cyanide,  NaCN.  Such  a  fixation  of  nitrogen  as  a  metal  cyanide  had 
been  accomplished  by  Thompson  as  early  as  1839  by  heating  together 
potassium  carbonate,  K2CO3,  carbon,  C,  and  atmospheric  nitrogen  gas 
in  the  presence  of  iron.  The  process  as  originally  carried  out  proved 
not  to  be  successful  and  up  to  1917  no  successful  process  for  converting 
atmospheric  nitrogen  into  metal  cyanides  was  in  operation.  Bucher 
recognized  the  important  role  of  metallic  iron  as  a  catalytic  agent  and 
developed  Thompson's  method,  fixing  the  nitrogen  of  the  air  according 
to  the  following  reaction  including  the  energy  factor. 

Na2CO3  +  4C  +  N2  — >        2NaCN  +  3CO  -  138,500  cal. 

Sodium 
cyanide 

The  energy  required,  represented  by  138,500  cal.,  is  counterbalanced 
by  the  energy  obtained  in  burning  the  carbon  monoxide  produced, 
which  amounts  to  +200,000  cal.,  so  that  the  total  energy  reaction  is  an 
exothermic  one.  The  result  was  obtained  by  using  either  air,  pure 


424  ORGANIC  CHEMISTRY 

nitrogen  gas  or  producer  gas.  At  the  present  time  the  process  is  being 
perfected  industrially  and  bids  fair  to  be  another  successful  method  of 
fixing  the  nitrogen  of  the  atmosphere.  Further  details  may  be  found 
in  the  original  articles  in  Jour.  Ind.  &  Eng.  Chem.,  9,  233  (1917).  The 
process  is  valuable  not  only  in  producing  sodium  cyanide,  which  has  a 
certain  value  of  its  own,  but  from  the  fact  that  from  the  cyanide  other 
products  are  able  to  be  obtained.  Some  of  the  possible  products  are 
the  following,  all  of  which  have  important  uses  in  the  industries  or  as 
fertilizers.  Sodium  ferrocyanide,  Na4Fe(CN)6,  sodium  hydroxide, 
NaOH,  ammonia  NH3  from  which  nitric  acid,  HNO3,  may  be  obtained 
by  oxidation,  sodium  formate,  H— COONa,  sodium,  Na,  cyanogen, 
(CN)2,  oxamide,  H2N— OC— CO— NH2,  oxalic  acid,  HOOC— COOH, 
sodium  cyanate,  NaOCN,  ammonium  cyanate,  NH4OCN,  and  urea, 
OC(NH2)2-  The  reactions  involved  in  these  transformations  have  all 
been  considered  previously  in  this  chapter  or  will  be  discussed  in  the 
following  chapter  in  connection  with  urea. 


XIII.  CARBONIC  ACID,  UREA,  URIC  ACID,  PURINE  BASES,  ETC. 
A.  CARBONIC  ACID  AND  DERIVATIVES 

CARBONIC  ACID 

It  may  appear  strange  at  the  outset  that  the  two  compounds 
carbonic  acid  and  urea  should  be  considered  together.  Carbonic  acid 
we  have  always  looked  upon  as  inorganic,  while  urea,  which  is  the  pro- 
duct of  living  animals,  seems  purely  organic.  The  fact  that  these  two 
compounds  are  very  definitely  related  emphasizes  the  statement  made 
at  the  beginning  that  the  characterization  of  a  compound  as  inorganic 
or  organic  rests  upon  facts  of  constitution  and  relationship  and  not 
upon  those  of  natural  occurrence.  It  also  shows  that  the  line  of 
demarcation  between  these  two  large  classes  of  compounds  is  an  indefi- 
nite thing  for  the  same  compound  may  rationally  be  considered  as 
belonging  to  both. 

Carbonates. — Our  acquaintance  with  carbonic  acid  as  an  inorganic 
compound  has  been  through  the  salts  which  it  forms  with  the  metals 
and  which  in  general  are  found  abundantly  in  the  earth's  crust,  e.g., 
sodium  carbonate,  Na2CO3;  calcium  carbonate,  CaCO3,  silver 
carbonate,  Ag2CO3,  etc. 

Carbonic  Acid. — These  salts  are  derived  from  the  acid  which  we 
term  carbonic  acid  and  to  which  the  formula  H2CO3  has  been  assigned. 
It  has  never  been  isolated  but  is  considered  to  be  the  product  of  the 
reaction  between  the  oxide  of  carbon,  carbon  dioxide,  CO2,  and  water 
just  as  sulphuric,  nitric  and  phosphoric  acids  are  the  products  of  the 
reaction  between  water  and  the  oxides  of  sulphur,  nitrogen  and  phos- 
phorus. 

Carbon  Dioxide. — The  fact  that  carbon  dioxide  contains  the  element 
carbon  and  that  it  is  the  result  of  the  oxidation  of  the  constituents  of 
living  animals  or  plants  and  also  of  the  oxidation  of  hydrocarbons 
such  as  methane  (p.  5)  may  be  considered  as  the  basis  for  the  possible 
classification  of  it  as  an  organic  compound.  This,  however,  is  not  the 
sole  reason  nor  even  the  more  important  reason  for  the  classification 
of  carbonic  acid  as  an  organic  compound. 

Constitution. — When  we  attempt  to  establish  the  constitution  of 
carbonic  acid  we  shall  find  additional  facts  which  show  that  in  its 

425 


426  ORGANIC  CHEMISTRY 

relationship  it  belongs  with  the  organic  compounds  though  it  is  not  so 
directly  a  derivative  of  the  hydrocarbons  as  some  other  organic  com- 
pounds such  as  alcohols,  acids,  etc. 

Carbonyl  Chloride. — The  simplest  proof  of  the  constitution  of  the 
hypothetical  substance  carbonic  acid,  H2CO3,  is  through  the  synthesis 
of  its  salts  and  esters  from  carbonyl  chloride  or  phosgene,  COC12. 
This  latter  compound  is  the  product  of  the  reaction  of  the  lower  oxide 
of  carbon,  viz.,  carbon  monoxide,  CO,  with  chlorine  in  the  sunlight  or 
in  the  presence  of  a  carbon  catalyser. 

CO      +      C12        >        COC12 

Carbon  Carbonyl  chloride 

monoxide  Phosgene 

Whether  we  consider,  in  this  reaction,  that  the  bivalent  carbon  of 
carbon  monoxide  is  changed  by  the  addition  of  two  chlorine  atoms  to 
tetravalent  carbon  of  carbonyl  chloride,  or  that  carbon  monoxide  is  an 
unsaturated  compound  of  tetravalent  carbon  which  by  addition  of  two 
chlorine  atoms  forms  the  saturated  compound  carbonyl  chloride,  or  that 
in  carbon  monoxide  oxygen  is  tetravalent  and  becomes  bivalent  in  carbonyl 
chloride,  whichever  view  is  held,  it  is  undoubtedly  the  fact  that  in 
carbonyl  chloride  the  carbon  is  tetravalent  and  the  constitution  is 

Cl 

Cl 

This  constitution  of  carbonyl  chloride  is  upheld  by  other  syntheses  as 
follows:  When  carbon  tetrachloride  and  carbon  dioxide  are  passed 
over  pumice  stone  heated  to  400°  carbonyl  chloride  is  obtained. 

CC14      +      C02        >         2COC12 

Carbon  Carbonyl 

tetra-  chloride 

chloride 

Also  when  carbon  tetrachloride  is  heated  with  sulphur  trioxide  or  with 
phosphorus  pentoxide  to  200°  it  yields  carbonyl  chloride  by  the  re- 
placement of  two  chlorine  atoms  by  oxygen  in  one  molecule  of  the 
tetrachloride  and  all  of  the  chlorine  atoms  by  oxygen  in  the  other 
molecule,  yielding  carbon  dioxide  also. 

2CC14      +      P2O5  — >'       COC12      +      2POC13      +      CO2 

Carbon  Carbonyl 

tetra-chloride  chloride 


CARBONIC   ACID   AND    DERIVATIVES  427 

If  different  proportions  are  used  no  carbonyl  chloride  is  obtained  but  all 
of  the  chlorine  of  carbon  tetrachloride  is  replaced  by  oxygen  and  carbon 
dioxide  alone  results. 

3  CC14      +      2P205  ~>        3C02      +      4POC13 

Also  chloroform  when  oxidized  with  potassium  bichromate  yields 
carbonyl  chloride  and  chlorine. 

2CHC13      +      30 >        2COC12      +      H2O      +      C12 

Chloroform  Carbonyl 

chloride 

Now  when  carbonyl  chloride  is  passed  into  ethyl  alcohol  an  ethoxy 
group  replaces  one  chlorine  atom  as  follows : 

/(Cl      H)OC2H5  /O— C2H5 


—  =  orCl—  COOC2H5 

XC1  XC1 

Carbonyl  Ethyl  chlor  formate 

chloride 

Ethyl  Chlor  Formate.  —  The  compound  formed  is  an  ethyl  ester  of 
chlor  formic  acid,  and  indicates  that  carbonyl  chloride  is  the  acid  chloride 
of  chlor  formic  acid.  By  further  action  of  sodium  alcoholate,  however, 
the  second  chlorine  atom  is  replaced  by  the  ethoxy  group. 


(C1  +  H)O—  C2H5  OC2H5 

Ethyl  chlor  formate  Di-ethyl  carbonate 

Di-ethyl  Carbonate.  —  This  product  is  a  di-ethyl  ester  of  carbonic 
acid,  as  is  proven  by  the  fact  that  it  is  also  obtained  when  silver  car- 
bonate, Ag2CO3,  reacts  with  two  molecules  of  ethyl  iodide  or  chloride. 

0(Ag       Cl)—  C2H5  XOC2H5 

Ag2C03  or  O  =  C<(  +  -  >     O  =  C<?  +  2  AgCl 

X0(Ag      Cl)—  C2H5  XOC2H5 

Silver  carbonate  Di-ethyl  carbonate 

(Di-ester  of  carbonic  acid) 

These  reactions  prove  that  carbonyl  chloride,  as  the  name  indicates,  is 
the  di-acid  chloride  of  carbonic  acid.    This  is  also  proven  by  the  fact 


428  ORGANIC  CHEMISTRY 

that  sodium  carbonate  with  phosphorus  pentachloride  yields  the  acid 
chloride. 

ONa  /Cl 

-r>     O  =  C<         +    2NaCl    +    2POC13 


Sodium  carbonate  Carbonyl  chloride 

(Di-acid  chloride 
of  carbonic  acid) 

These  reactions  prove  that  silver  carbonate  must  have  the  constitution 
given  to  it  above;  that  the  acid  from  which  it  is  derived,  the  unisolated 
carbonic  acid,  has  the  corresponding  constitution;  that  the  di-ethyl 
compound,  formed  from  carbonyl  chloride,  is  a  di-ethyl  ester  of  carbonic 
acid;  and  carbonyl  chloride  is  the  di-acid  chloride  of  carbonic  acid,  as 
follows: 

/OAg  /OH  /Cl  /OC2H5 

o=c  o=c  o=c  o=c 


Silver  Carbonic  Carbonyl  Di-ethyl  ester 

carbonate  acid  chloride  of  carbonic  acid 

We  see,  therefore,  that  carbonyl  chloride  may  be  considered  as  either 
the  mono-acid  chloride  of  chlor  formic  acid  or  the  di-acid  chloride  of 
carbonic  acid,  which  means  that  carbonic  acid  may  also  be  considered 
as  hydroxy  formic  acid.  The  following  formulas  show  this  relation- 
ship 

'        H  Cl  OH 


\)H  \)H 


Formic  Chlor  formic  Carbonic  acid. 

acid  acid  Hydroxy  formic 

acid 

Cl 

o=c( 

XC1 

Carbonyl  chloride  or  Chlor  formyl  chloride 

(di-acid  chloride  (acid  chloride  of 

of  carbonic  acid)  chlor  formic  acid) 

Thus  while  carbonic  acid  itself,  having  never  been  isolated,  is  still  a 
hypothetical  substance,  we  know,  beyond  all  doubt,  the  constitution 
of  its  salts,  esters  and  acid  chlorides;  so  that  the  constitution  of  the  un- 


UREA    AND    DERIVATIVES  429 

known  compound  is  likewise  established.  The  constitution  agrees 
with  the  fact  that  carbonic  acid  is  a  dibasic  acid.  As  an  organic  acid 
it  contains  a  carboxyl  group  and,  though  it  does  not  contain  two  such 
groups,  it  contains  two  hydrogens  both  of  which  are  in  hydroxyl  combina- 
tion as  part  of  a  carboxyl  group.  This  is  analogous  to  water  which, 
though  it  contains  really  only  one  hydroxyl,  yet  both  hydrogens  exist 
in  hydroxyl  combination. 


H—  o—  H 


Carbonic  acid  Water 

(2  carboxyl  hydroxyls)  (2  hydroxyl  hydrogens) 

Phosgene.  —  One  more  fact  in  connection  with  carbonyl  chloride. 
This  compound,  known  also  as  phosgene  gas,  is  a  volatile  liquid  boil- 
ing at  8°.  It  is  one  of  the  war  gases  used  in  the  recent  war.  It  is  a 
vile  smelling  poisonous  substance  and  was  used  in  shells  and  bombs, 
also  as  a  drift  gas. 

B.  UREA  AND  DERIVATIVES 

NH2 
Urea  O  =  C<  Carbamide 


Urea,  the  principal  constituent  of  animal  urine,  is  important  not  only 
physiologically,  but  also  historically.  Until  1828  the  compound  was 
known  only  as  the  product  of  animal  life.  In  this  year  Wohler  syn- 
thesized it  from  an  ordinarily  considered  inorganic  substance  which 
could  be  made  from  the  elements.  This  substance  was  ammonium 
cyanate,  and  Wohler  found  that  by  simply  evaporating  a  solution  of 
it  a  complete  transformation  into  urea  was  effected.  The  composi- 
tion formulas  of  the  two  compounds  are  the  same,  viz.,  CH4ON2,  i.e., 
they  are  isomeric.  The  synthesis  of  Wohler  shows  nothing  in  regard 
to  the  relationship  of  the  two  compounds  as  to  structure.  It  was  of 
extreme  importance  because  it  was  the  first  instance  of  a  purely 
organic  substance  being  prepared  from  elemental  or  inorganic 
materials. 


430  ORGANIC  CHEMISTRY 

Carbamide. — The  constitution  of  urea  is  shown  by  its  synthesis 
from  carbonyl  chloride  and  ammonia. 

,(C1         H)— NH2  xNH2 

O  =  (/  _|_  ^        O  =  C  4-  2HC1 

\C1         H)— NH2  \NH2 

Carbonyl  chloride  Urea  or  carbamide 

Urea  is  thus  the  di-amide  of  carbonic  acid  and  is  also  termed  carbamide. 
It  corresponds  to  carbonyl  chloride,  the  di-acid  chloride  of  carbonic 
acid.  The  same  constitution  is  proven  in  a  similar  manner  by  the 
synthesis  of  urea  from  di-ethyl  carbonate  by  the  action  of  ammonia. 

I5        H)— NH2  yNH2 

+  — >     O  =  C/         +  2C2H5OH 

>(OC2H5        H)— NH2  XNH2 

Di-ethyl  carbonate  Urea 

Carbamic  Acid. — It  will  be  recalled  that  oxalic  acid,  the  simplest 
dicarboxylic  acid,  yields  a  corresponding  di:amide  and  that  there  is  also 
formed  an  intermediate  product  known  as  oxamic  acid. 

COOH         CONH2         CONH2 
COOH         COOH          CONH2 

Oxalic  acid  Oxamic  acid  Oxamide 

A  similar  compound,  viz.,  carbamic  acid,  stands  intermediate  be- 
tween carbonic  acid  and  carbamide  (urea) .  It  is  not  known,  however, 
as  such  but  as  the  ammonium  salt  or  as  an  ester. 


/NH2  /. 

.               ^^              OC'                OC/  OC( 

XOH             XOH              XNH2             XONH4  XOC2H5 

Carbonic  acid       Carbamic  acid                Carbamide                  Ammonium  Ethyl  carbamate 
(not  isolated)                       urea                        carbamate 

Ammonium  carbamate   is  made  by  the  action  of  ammonia  and 
carbon  dioxide 


0  =  c  =  O  +  H— NH2  -— >  0  =  C 

XOH  ONH4 

Carbamic  Ammonium 

acid  carbamate 

(not  isolated) 

This-reaction  is  similar  to  that  which  takes  place  when  ammonia  forms 

an  addition  product  with  aldehydes,  e.g.,  ammonium  acetaldehyde 


UREA    AND    DERIVATIVES  431 

(p.  1  1  6).    Ethyl  carbamate  is  formed  by  the  action  of  ammonia  upon 
ethl  chlor  formate. 


XOC2H 


H)—  NH2 

+  ->      b- 


XOC2H5 


Ethyl  Ethyl  carbamate 

chlor  formate  Urethane 

Urethane.  —  This  ethyl  ester  of  carbamic  acid  is  known  as  urethane. 
Ammonium  carbamate  is  the  intermediate  product  in  the  relationship 
between  ammonium  carbonate  and  carbamide,  analogous  to  that 
between  ammonium  acetate  and  acetamide. 

-H2O 
CHs—  CO(O)NH2(H2)        ;ZZ!        CH3—  CO—  NH2 

Ammonium  acetate  TT  (~\\  Acetamide 

H2O  +  CO2  -f  2NH3  -» 


/(O)NH2(H2)   -H?O  /NH2  -H2O 

o=c(  ~^i  o=c\  z=io=c 

\)NH4  H2O+  X(O)NH2(H2)  H2O+  XNH2 

Ammonium  Ammonium  Carbamide 

carbonate  carbamate  Urea 

As  ammonium  carbonate  is  formed  by  the  action  of  ammonia  and  car- 
bon dioxide  this  relationship  agrees  with  the  formation  of  ammonium 
carbamate  just  referred  to. 

Biological  Synthesis  and  Decomposition.  —  This  relationship  be- 
tween urea  and  ammonium  carbonate  (ammonia  and  carbon  dioxide) 
is  of  especial  importance  because  it  is  concerned  as  a  reversible  reaction 
both  in  the  synthesis  of  urea  in  the  animal  body  and  in  the  decomposi- 
tion of  urea  in  the  soil.  It  is  at  least  possible  that  the  formation  of  urea 
in  the  animal  body  takes  place,  by  the  steps  represented  in  the  above 
relationship,  from  ammonia  and  carbon  dioxide  both  of  which  are 
produced  by  the  katabolic  hydrolysis  and  oxidation  of  proteins.  The 
reverse  reaction,  viz.,  the  decomposition  of  urea  into  ammonia  and  car- 
bon dioxide  is  taking  place  continually  whenever  urea  in  manure  is 
being  decomposed.  In  this  way  the  greater  part  of  the  nitrogen  of 
protein  food  is  returned  to  the  soil  to  be  used  as  plant  soil  food. 

If  we  consider  together  the  facts  which  we  have  presented  in  regard 
to  urea  and  carbamic  acid  we  will  realize  that  they  are  directly  related 
to  both  carbonic  acid  and  formic  acid.  The  following  schematic  repre- 
sentation of  these  relationships  will  make  this  clear. 


432 

CO     +  C12 

Sn 
mon- 

oxide 

OH 

0=C<( 

OH 

Carbonic 
acid 


ORGANIC  CHEMISTRY 

Cl  OC2H5 

=  C<  -^O  = 

C1 


Carbonyl 
chloride 


OAg 


OAg 

Silver 

carbonate 


H 

H—  COOH  or  O  =  C^  —  »O  = 

\OH 


Formic  acid 


Ethyl  chlor 
formate 


OC2H6 


OC2H5 
Di-ethyl 
carbonate 


OH 


QH 

Hydroxy 
formic 

acid 
Carbonic 

acid 


--  O  =  C 


NH 


OC2H5 

Ethyl  ester 

of  carbamic 

acid 


NH2 


NH2 

Car- 

bamide 

Urea 


NH2  NH2 

~>O  =  C\ 
\ 


>H 

Amino 

formic 

acid 

Carbamic 
acid 


Amino 

for  ma- 

mide 

Urea 


H2N—  COOH 
Amino  formic  acid 


H2N— CN 
Cyan  amide 

Nitrile  of 
amino  formic  acid 

Thus  carbamic  acid  may  be  considered  either  as  amino  formic  acid 
or  as  the  mon-amide  of  carbonic  acid,  i.e.,  carbamic  acid ;  and  urea  may 
similarly  be  considered  as  the  amide  of  amino  formic  acid  or  as  the  di- 
amide  of  carbonic  acid,  i.e.,  carbamide. 

Wohler's  Synthesis. — From  the  preceding  discussion  of  the  consti- 
tution of  urea  and  of  ammonium  cyanate  (p.  418)  we  can  express  the 
transformation  involved  in  Wohler's  synthesis  of  urea  by  the  following 
rearrangement. 

NH2 


H4N— O— C  =  N 

Ammonium 
cyanate 

H2)H2N— O— C  =  N 

Ammonium 
cyanate 


,/ 
•\ 


or 


NH2 

Urea 


H2N—  C— NH2 
O 

Urea 


UREA   AND   DERIVATIVES  433 

Recalling  the  methods  of  preparing  hydrogen  cyanide,  we  see  how  we 
may  say,  that,  in  Wohler's  synthesis,  an  animal  substance  was  made 
from  elemental  constituents  by  laboratory  methods. 

Electric  arc 

C  +  N  ~?        NC— CN 

Cyanogen 


2KOH  +  NC—  CN        -  >        KCN  +  KOCN  +  H2O 

otassiu 
cyanate 


t  Cyanogen  i     f^         Potassium 


K2  +  H20 

T 

H2  +  O  '  KOCN 

/NH2 
r\  —  r*/ 


(NH4)2SO4  +  KOCN     >    NH4OCN 

.mmoniu 
cyanate 


Ammonium  "MTT 


Urea 

2NH3      4-      H2SO4 
Electric  j 
arc 


3H2 


0 


In  the  synthesis  of  urea  from  ammonium  cyanate  the  cyanate  may  be 
used  as  such  already  prepared  or  it  mav  be  obtained  from  ferro-cyanides 
or  cyanides  by  the  transformations  already  given  (p.  416). 

Protein 
+  K2CO3  -  -»  K4Fe(CN)6  +  K2CO3  +  heat  -  -+  sKCN  +  KOCN 


+  iron  +  CO2       +  Fe 

or 

K4Fe(CN)6  +  K2Cr2O7  +  heat  —  *        6KOCN 

boiling  yNH2 

KOCN  +  (NH4)2S04  -+        NH4OCN  -j        OC<^ 

solution  NH2 

Urea 


434  ORGANIC  CHEMISTRY 

Occurrence  and  Properties. — Urea  occurs  as  a  normal  constituent 
in  animal  urine  to  the  amount  of  about  2  per  cent  in  man.  It  was 
discovered  in  1773.  Its  physiological  significance  will  be  considered 
later.  It  is  also  found  in  small  amounts  in  the  blood  and  lymph  of 
animals.  In  the  blood  of  sharks  it  is  present  in  as  large  amounts  as 
in  human  urine.  Urea  is  a  beautifully  crystalline  solid  easily  soluble 
in  water  and  in  alcohol.  It  melts  at  i32°-i33°  and  sublimes  in  a 
vacuum  at  i2O°-i3O°. 

Biuret. — On  further  heating  in  the  air  it  decomposes  yielding  car- 
bon dioxide,  ammonia,  and  an  interesting  body  known  as  biuret.  The 
last  compound  has  the  constitution  shown  by  the  following  reaction. 
It  is  formed  from  urea  by  the  loss  of  one  molecule  of  ammonia  from  two 
molecules  of  urea.  The  significance  of  the  name  biuret  is  apparent 
from  the  reaction. 

NH2  NH2 

OC<" 

NH(H)        —  NH3  /NH 

OG 


(NH2)  NH2 

/  Biuret 


Urea  (2  mol.) 

Also  when  urea  loses  one  molecule  of  ammonia  from  one  molecule  of  urea 
by  the  action  of  phosphorus  pentoxide  we  obtain  cyanuric  acid  and 
iso-cyanic  acid  (p.  418). 

,NH(H 

C<  —  >        O  =  C  =  NH  and  (OCNH)3 

yanur 
acid 


YNH  Iso-cyanic  acid  Cyanuric 


Urea 

When  boiled  with  acid  or  alkalies  urea  is  decomposed  into  carbon 
dioxide  and  ammonia 


+  H20  —  >  -      CO,  +  2NHS 

NH2 


Urea 


Enzymatic  Hydrolysis.  —  This  is  a  simple  hydrolytic  reaction  and  is 
also  brought  about  by  enzymes  and  bacteria,  so  that  when  urine  de- 


UREA   AND    DERIVATIVES  435 

composes  by  fermentation  in  piles  of  animal  manure  the  urea  yields 
carbon  dioxide  and  ammonia  which  of  course  yield  ammonium  car- 
bonate. The  relation  of  urea  to  ammonium  carbonate  has  been  dis- 
cussed (p.  431). 

Hypobromite  Reaction.  —  When  treated  with  hypobromites  or 
nitrous  acid  urea  is  oxidized  and  carbon  dioxide  water  and  nitrogen  gas 
are  obtained. 


OCC  +  3NaOBr  —  *        CO2  +  2H2O  +  N2 

NH2 

or 
Br 

/N(H2      O)—  Na 
Na—  (O  +  OC)^  +  -»  2H20  +  C02  +  N2  +  3NaBr 

XN(H2      O)—  Na 
Br  | 

Br 

In  this  reaction  all  of  the  nitrogen  gas  is  set  free,  quantitatively,  one 
molecule  of  nitrogen  per  one  molecule  of  urea,  (i.e.]  60  parts  urea  (mol. 
wt.  urea  =  60)  yield  28  parts  nitrogen  (mol.  wt.  N.  =  28). 
With  nitrous  acid  twice  the  amount  of  nitrogen  is  obtained. 

N(H2       O)N(OH) 
OC<(  +  ->        C02  +  3H20  +  2N2 

XN(H2       0)N(0)(H) 

Clinical  Test.  —  By  these  reactions,  which  are  easily  carried  out  by 
simply  adding  a  sodium  hypobromite  solution  to  a  solution  of  urea 
(urine),  the  per  cent  of  urea  in  urine  may  be  determined.  The 
volume  of  the  nitrogen  gas  evolved  may  be  readily  measured  and  from 
this  the  weight  calculated.  Apparatus  made  especially  for  this  pur- 
pose, in  which  the  volume  of  nitrogen  gas  evolved  is  read  directly  in 
per  cent  urea  in  the  urine,  are  termed  ureometers  and  give  us  simple 
clinical  means  of  analyzing  urine  for  urea.  The  sodium  hypobromite 
solution  is  made  up  alkaline  so  that  the  carbon  dioxide  which  is  also 
evolved  is  absorbed,  the  nitrogen  only  remaining  as  a  gas. 


436  ORGANIC  CHEMISTRY 

By  heating  with  alcoholic  potassium  hydroxide  urea  yields  potas- 
sium cyanate. 


OC<  +  KOH        -  >        KOCN  +  NH3  +  H2O 

\XTTT  Potassium 


cyanate 
Urea 

This  is  really  the  reverse  of  Wohler's  synthesis  as  ammonium  cyanate 
may  be  considered  as  first  formed. 

Salts.  —  Urea  being  a  di-amide  or  an  amino  amide  forms  salts  with 
acids,  in  which  only  one  amino  group  is  neutralized. 

NH2HNO3  NH2HOOC  H2N 

OC<(  OC<^  |  )>CO 

XNH2  XNH2          COOHH2N 

Urea  nitrate  Urea  oxalate 

Isolation  from  Urine.  —  Urea  may  be  easily  isolated  from  urine  by 
first  converting  it  into  the  nitrate  which  is  much  less  soluble  and  there- 
fore crystallizes  out.  Urine  is  evaporated  to  a  thin  syrup  and  concen- 
trated nitric  acid  added  when  urea  nitrate  separates  in  abundant 
crystals.  These  are  purified  by  recrystallization  and  decolorization 
and  then  decomposed  with  barium  hydroxide. 

NH2  NH2—  HNO3 

HNO3    -  >     2OC<^  +  Ba(OH)2       -4 

NH2  NNH2 

Urea  (in  urine)  Urea  nitrate 


+  Ba(NO3)2 
NH2 

Urea 

Alkyl  Ureas.  —  By  substituting  alkyl  amines  for  ammonia  in  the 
reaction  for  the  synthesis  of  urea  from  carbonyl  chloride,  or  by  using 
alkyl  derivatives  of  ammonium  cyanate  (cyanic  acid  salts  of  alkyl 
amines)  ,  in  the  Wohler  synthesis,  alkyl  ureas  may  be  obtained.  They 
are  of  different  types  as  illustrated  by  the  following  formulas  showing 
their  relationship  to  urea. 


UREA   AND    DERIVATIVES 


437 


OC 


N(CH3)2 
N(CH3)2 


OC 


N(CH3)2 


Tetra-methyl 
urea 


Di- methyl  urea 

(unsymmelrical) 


,NH2 
XNH2 

Urea 


NHC 


NH2 

Mono -ethyl 
urea 


NHC2H5 


VNHC2H5 

Di -ethyl  urea 

(symmetrical) 


,N(C2H5)2 
<" 
XNHC2H5 


Tri -ethyl 
urea 


Thio-ureas 

Thio-ureas. — As  sulphur  may  replace  oxygen  in  carbon  dioxide, 
alcohol,  carbonyl  chloride  and  ammonium  cyanate  yielding  correspond- 
ing thio  compounds,  so  also  there  are  sulphur  analogues  of  urea  known 
as  thio -ureas.  These  need  not  be  considered  more  than  to  give  the 
oxygen  and  sulphur  compounds  in  this  relationship. 

Thio-alcohol  (mercaptan) 
Carbon  di-sulphide 
Thionyl  chloride 
Ammonium  thio-cyanate 
Thio-urea 

Thio-carbamic  acid  ester 
Alkyl  thio-urea 


Ethyl  alcohol 
Carbon  dioxide 
Carbonyl  chloride 
Ammonium  cyanate 
Urea 
Carbamic  acid  ester 
Alkyl  urea 

C2H6—  OH 
CO* 
Cl—  CO—  Cl 
NH4—  0—  CN 
H2N—  CO—  NH2 
H2N—  CO—  OR 
RHN—  CO—  NHR 

C2H5—  SH 
CSj 
Cl—  CS—  Cl 
NH4—  S—  CN 
H2N—  CS—  NH2 
H2N—  CS—  OR 
RHN—  CS—  NHR 

Ureids 


As  an  amino  compound  urea  acts  with  acetyl  chloride  or  acetic 
anhydride  or  other  acyl-chlorides  or  anhydrides  forming  acyl  deriva- 
tives analogous  to  acetamide.  These  compounds  are  termed  ureids. 


OC 


NH2(H 

Ammonia 

,NH(H 


NH2 

Urea 


OC( 

XNH(H 

Mono  -acetyl  urea 

(a  ureid) 


Cl)— OC— CH3 

Acetyl  chloride 

Cl)— OC— CH3 


—  CH 


Cl)—  OC—  CH 


NH2— OC— CH3 

Acetamide 


,NH— OC— CH3 


oc: 


— OC— CHj 

Di-acetyl  urea 
(a  ureid) 


ORGANIC  CHEMISTRY 


Cyclic  Ureids. — With  chlorides  of  di-basic  acids,  or  of  hydroxy 
mono-basic  acids,  the  double  acyl  group  unites  with  the  two  amino 
residues  of  urea  forming  a  cyclic  ureid  as  follows : 

,NH(H        Cl)— OC  /NH— OC 


OC 


/J 
\ 


— ->    OC( 


NH(H 

Urea 


Cl)— OC 

Oxalyl 
chloride 


XNH— OC 

Oxalyl  urea 

(cyclic   ureid) 


Several  of  these  cyclic  ureids  are  of  especial  importance  in  connection 
with  uric  acid  which  we  shall  presently  discuss.     These  are  as  follows: 


OC 


NH— CO 


from 


NH— CO 


Oxalyl  urea 
Parabanic  acid 


NH— CH2 


oc( 


from 


Glycolyl  urea 
Hydantoin 


NH— CO 

>lyl  urea 
lantoin 

/NH— CO 

I 
OC\  CH2        from 

NH— CO 

Malonyl  urea 
Barbituric  acid 

/NH— CO 

/         '    I 
OC(  CH(OH)     from 

\NH-CO 

Tartronyl  urea 
Di-aluric  acid 

/NH— CO 

OC<  C(OH) 

II 
NH— C(OH) 

Iso-dialuric  acid 


HO— CO 


HO— CO 

Oxalic 
acid 

HO— CH; 


HO— CO 

Glycolic  acid 

HO— CO 


CH2 
HO— CO 

Malonic  acid 

HO— CO 

CH— OH 


HO— CO 

Tartronic  acid 


UREA    AND  DERIVATIVES                                          439 

NH— CO  HO— CO 

OC                 C(OH)2  from                   C(OH)2 

NH— CO  HO— CO 

Mesoxalyl  urea  Mesoxalic  acid 
Alloxan 

NH-CH-NH,  HO-CH-OH    HC  =  O 


OC; 


CO    from 


or 


HO-CO  CO-OH 

L — CO      JNH2  Glyoxylic 

Glyoxylyl  di-urea  acid 

Allantoin  (a  di-ureid) 

These  compounds  need  not  be  discussed  further  than  to  show  their 
relationships  as  above. 

Imino  Derivatives  of  Urea 

The  imino  group  ( =  NH) ,  the  bivalent  ammonia  radical,  corresponds 
to  bivalent  oxygen  and  compounds  result  from  the  replacement  of 
carbonyl  oxygen  with  this  imino  radical.  We  have,  for  example,  imino 
esters  and  imino  acid  amides. 

CH3— CO— OC2H5  CH3— C(NH)— OC2H5 

Ester  Imino-ester 

CH3— CO— NH2  CH3— C  (NH)— NH2 

Acid  amide  Imino  acid  amide 

(amidine) 

In  urea  the  carbonyl  oxygen  is  thus  replaced  by  the  imino  group  and 
an  imino  urea  is  obtained. 

NH2  /NH 

XNH2 

Guanidine,  Guanine,  Guano. — This  compound  is  known  as  guani- 
dine.  It  is  obtained  from  a  related  compound  known  as  guanine 
(p.  449),  which  is  one  of  the  nitrogenous  compounds  present  in  guano, 
a  geological  deposit  of  bird  excrement  and  bird  remains.  Guano  was 
at  one  time  a  valuable  phosphate  and  nitrogen  fertilizer.  Guanidine 
has  been  prepared  by  analogous  reactions  to  those  used  for  the  synthe- 
sis of  urea,  thus  showing  its  relationship  to  urea,  carbonic  acid  and 


440  ORGANIC  CHEMISTRY 

carbonyl  chloride.     It  is  formed  by  the  more  complete  reaction  of 
ammonia  upon  carbonyl  chloride  or  upon  carbonic  acid  esters. 


+  2H)NH2       ->    0)  =  C(  +  HN(H2 

C\  ^KH2 

Carbonyl  chloride  Urea 

/NH 


XNH2 

Guanidine 

/OC2H5  /NHt 

O  =  C/  H-  3NH3  — »        HN  =  C/ 

XOC2H5  XNH2 

Di-ethyl  carbonate 

The  most  important  synthesis  of  the  compound  is  that  from  cyan- 
amide  by  the  direct  addition  of  ammonia,  when  heated  in  alcoholic 
solution  with  ammonium  chloride. 

N  SE  C— NH2  +  H— NH2        >        HN  =  C/ 

Cyanamide  \ 

Guanidine 

Similar  to  this  last  synthesis  is  that  from  cyanogen  iodide  and  ammonia. 


H)—  NH2 

N  =  C(I  +  --  >        HN  =  C(;  +  HI 

CIoadidgeen         H-NH2  XNH2 

Guanidine 

Guanidine  is  a  soluble,  crystalline  compound  and  acts  as  a  very  strong 
base,  as  would  be  expected  from  the  fact  that  it  contains  three  am- 
monia residues,  one  of  which,  as  an  imino  group,  is  in  place  of  a  carbonyl 
oxygen  in  urea  or  in  carbonic  acid.  It  readily  absorbs  carbon  dioxide 
from  the  air.  It  is  decomposed  by  barium  hydroxide  into  urea  and 
ammonia. 


(Ba(OH)2) 

+  H2)0  0  =  C  +     NH, 

NH2  XNH2        Ammonia 

Guanidine  Urea 

Being  basic  it  forms  salts  with  acids  analogous  to  the  urea  salts. 


UREA   AND    DERIVATIVES  441 

Semi-carbazid.  —  When  guanidine  is  nitrated,  by  means  of  a  mixture 
of  nitric  and  sulphuric  acids,  a  nitro  guanidine  is  obtained,  which,  on 
reduction,  yields  amino  guanidine,  and  this,  on  boiling  with  dilute 
acids  or  alkalies,  yields  a  compound  known  as  semi-carbazid.  This  in 
turn  breaks  down  into  ammonia,  hydrazine  (di-amine)  and  water. 

NH(H      HO)—  NO2  /NH—  N02 

/  +  H       -» 

NH2  XNH2 

Guanidine  Nitro  guanidine 

NH—  NH2 

+H2O       —  > 


Amino  guanidine 

/NH—  NH2 
0  =  C<;  +  H)—  O—  (H       ->    NH3  +  C02  +  H2N—  NH2 

\NH2  Hydrazine 

Semi-carbazid 

Semi-carbazid  is  an  important  reagent  forming  derivatives  with  alde- 
hydes and  ketones.  Its  name  indicates  that  it  is  a  hydrazine  derivative 
of  carbonic  acid  or  of  carbamic  acid.  It  is  also  amino  urea. 

/OH  /OH  /NH—  NH2  /NH2 

0  =  C<  0  =  CX  0  =  CC  0  =  C( 


,  NNH2  NNH2  NNH2 

Carbonic  acid  Carbamic  acid  Semi-carbazid  Urea 

Amino  urea 

Corresponding  to  the  ureids  derived  from  urea  by  the  action  of 
acid  chlorides,  we  have  guanidids  derived  from  guanidine  by  the  same 
action. 

/NH— CH2  /NH— CH2 


XNH— CO  NH— CO 

Hydantoin.     Glycolyl  urea  Glycolyl  guanidine 

(ureid)  (guanidid) 

Creatine  and  Creatinine. — This  particular  guanidid  is  important 
because  the  methyl  derivative  of  it  is  a  substance  found  in  urine  and 


442  ORGANIC  CHEMISTRY 

known  as  creatine.  The  non-cyclic  guanidid  corresponding  to  this 
is  known  as  creatinine. 

N(CH3)— CH2     +  H20  N(CH3)— CH2 

HN  =  C<^  |  "HI        HN=C<(  | 

XNH-     —CO       -H2O  XNH2          COOH 

Creatine  Creatinine 

Plainly  creatinine  is  the  hydrate  of  creatine  or,  vice  versa,  creatine  is  the 
anhydride  of  creatinine.  Both  of  these  compounds  are  found  in  urine 
associated  with  urea  as  metabolic  products  of  proteins. 

C.  URIC  ACID 

Uric  acid  is  associated  with  urea,  creatine  and  creatinine  in  urine. 
In  the  urine  of  mammals  it  occurs  in  small  amounts,  the  chief  nitrogen 
compound  being  urea.  In  birds  and  reptiles,  however,  uric  acid  pre- 
dominates and  is  the  precursor  of  the  related  guanine  in  guano. 

Constitution. — The  constitution  of  uric  acid  has  been  established 
by  a  remarkable  set  of  syntheses  based  upon  a  study  of  the  products 
of  decomposition.  In  this  work  several  men  played  an  important  part. 
The  most  comprehensive  work  which  cleared  up  the  question  of  the 
constitution  not  only  of  uric  acid  but  of  several  related  compounds, 
which  we  shall  presently  consider,  was  by  Emil  Fischer,  whom  we  have 
already  mentioned  in  connection  with  two  other  groups  of  compounds 
intimately  connected  with  plants  and  animals,  viz.,  the  carbohydrates 
and  the  proteins  (p.  393).  Earlier  important  work  was  done  by 
Liebig  and  Wb'hler,  and  the  relationship  of  the  decomposition  products 
was  mainly  due  to  the  work  of  Baeyer.  The  accepted  formula  was  first 
suggested  by  Medicus,  and  the  syntheses  supporting  it  were  worked  out 
by  Horbaczewski,  and  by  Behrend  and  Roosen. 

One  of  the  first  facts  observed  in  regard  to  uric  acid  was  that  on 
heating  it  yielded  cyanuric  acid,  (OCNH)3,  and  ammonia,  NH3.  As 
these  same  products  had  been  obtained  by  heating  urea,  OC(NH2)2, 
it  was  considered  probable  that  a  urea  residue  was  present  in  uric  acid. 
It  was  then  shown  that  on  oxidation  with  lead  dioxide,  one  of  the 
ureids,  the  di-ureid  known  as  allantoin  was  obtained,  together  with 
urea,  oxalic  acid  and  carbon  dioxide.  With  other  oxidizing  agents, 
such  as  nitric  acid,  the  products  were  equal  molecules  of  urea  and  the 
two  ureids  alloxan  and  parabanic  acid.  From  alloxan  there  may  be 
obtained,  by  reduction,  two  other  ureids,  viz.,  barbituric  acid  and 


URIC   ACID 


443 


dialuric  acid.     The  established  constitution  of  these  ureids  (p.  438) 
gives  the  following  relationship. 


Oxidation 


(jxiaaiiun  / 

Uric  acid >        O  =  C<Q 

(PbO2) 


Uric  acid 


Oxidation 
(HNCh) 


,NH—  CH— HN 


X 


NH—  CO    H2N/ 
Allantoin 


/ 

\ 


.NH— CO 

C(OH)5 

NH— CO 
Alloxan 


/ 
»/ 


/NH2 

c<; 

XNH2 
Urea 


NH* 


COOH 

COOH 

Oxalic 

acid 


co2 


XNH2 
Urea 


/NH—  CO 

\ 
XNH— CO 

Parabanic   acid 


reduction 


NH— CO 
O  =  C<^  CH: 

^NH— CO 
Barbituric  acid 


O  =  C 


NH— CO 

CH(OH) 
NH— CO 


Dialuric  acid 

From  the  facts  that  uric  acid  yields  the  di-ureid  allantoin  and  also 
equal  molecules  of  alloxan,  a  mono-ureid,  and  urea  it  was  concluded 
that  uric  acid  must  contain  two  urea  residues.  From  the  constitution 
of  alloxan  and  its  reduction  products,  barbituric  and  dialuric  acids, 
uric  acid  must  likewise  contain  a  three  carbon  chain  linked  to  a  urea 
residue  by  the  end  carbon  atoms.  Also,  as  it  yields  parabanic  acid  or 
oxalyl  urea,  one  of  the  urea  residues  must  be  linked  to  two  adjacent  car- 
bon atoms  in  this  chain. 

Medicus'  Formula. — The  following  grouping  is  thus  indicated  and 
will  be  seen  to  be  present  in  the  formula  as  suggested  by  Medicus. 

,'  — C  NH  -CO 

Urea 
residue    \      C— }  O  =  C<f  \       C—     — HN, 


— C— 


Urea 
residue 


\ 


NH 


>C  = 


HN' 


Uric  acid     Medicus  formula 


'  The  splitting  of  the  compound  at  the  dotted  line  would  yield  al- 
loxan and  urea  while  splitting  at  the  broken  line  would  yield  parabanic 
acid  and  urea.  Confirmation  of  this  constitution  has  been  furnished 
in  two  ways:  (i)  by  Fischer's  study  of  the  methyl  substitution  prod- 
ucts of  uric  acid  and  (2)  by  the  syntheses  of  Horbaczewski  and  of 
Behrend  and  Roosen. 


444 


ORGANIC  CHEMISTRY 


Methyl  Uric  Acids,  Fischer. — Fischer  found  two  important  facts 
in  regard  to  the  methyl  uric  acids,  (a)  There  is  a  tetra -methyl  uric 
acid  in  which  each  methyl  group  is  linked  to  a  nitrogen  atom  so  that  there 
must  be  four  imino  hydrogen  atoms  in  uric  acid,  (b)  There  are  two 
isomeric  mono-methyl  uric  acids,  therefore,  two  of  the  imino  groups 
must  be  unlike,  i.e.  the  compound  must  be  unsymmetrical.  These 
compounds  are: 

,N(CH3)— CO  /NH CO 


C— N(CH3)          OC< 

II  k          /co 

N(CH3)— C— N(CH3r 

Tetra -methyl  uric  acid 


C— HN 


N(CH3)— C— 

Mono- methyl  uric  acid 

/NH— CO 


and  OC<  C— !HN 


\:o 


XNH— C— |N(CH3) 

Isomeric  mono-methyl 
uric  acid 

He  found  that  one  of  these  mono-methyl  uric  acids  yielded  methyl 
alloxan  and  urea,  whereas  the  other  yielded  methyl  urea  and  alloxan ; 
as  indicated  by  the  dotted  lines.  Therefore  uric  acid  is  a  di-ureid  of  an 
acid  as  represented  below,  the  ureid  being  formed  as  follows: 


,NH(H 


HO)— CO 


OC 


1 

XNH(H 

Urea 

V^            ^WJ-J. 

HO)—  C—  (OH 

Acid 

(hypothetical) 

\co 

H)HNX 

Urea 

NH— CO 


OC< 


C— HNN 


NH— C— HN 

Uric  acid 


Such  an  acid  is  not  known,  but  it  would  be  tri-hydroxy  acrylic  acid, 
C(OH)2  =  C(OH)— COOH,  fromCH2  =  CH— COOH,  acrylic  acid. 


URIC  ACID 


445 


Horbaczewski's  Synthesis.  —  The  syntheses  which  establish  the 
above  formula  are  several.  The  two  best  are  those  before  mentioned, 
of  Horbaczewski  and  of  Behrend  and  Roosen.  The  former  heated 
together  tri-chlor  lactic  amide  and  urea  and  obtained  uric  acid. 


OC( 


NH(H 


NH(H 

Urea 


Horbaczewski's  Synthesis 
NH2)CO 


C(H)(OH 

Cl)— C— (Cl 


(Cl) 

Tri-chlor 
lactic  amide 


H)HN, 


oc 


H)HN 

Urea 


NH— CO 
C— 


NH—  C— 

Uric  acid 


> 


o 


2HC1 
NH4C1 


+ 


Behrend  and  Roosen's  Synthesis.  —  The  latter  prepared  uric  acid 
by  heating  iso-dialuric  acid  and  urea  with  sulphuric  acid. 


Behrend  and  Roosen's  Synthesis 


OC 


,NH     CO 

I 
C(OH) 


NH—  C(OH) 

Iso-dialuric  acid 


H)HN 


H)HN 

Urea 


o 


NH—  CO 


OC 


C—  HN 


NH—  C— 

Uric  acid 


2H2O 


The  constitution  of  the  iso-dialuric  acid  was  established  by  its 
synthesis  from  aceto-acetic  ester  and  urea. 


446  ORGANIC  CHEMISTRY 

Properties. — Uric  acid  forms  colorless  crystals  which  are  only 
slightly  soluble  in  water.  One  part  requires  1900  parts  boiling  water 
and  10,000  parts  at  18.5°.  Therefore  in  urine  it  can  not  be  present  as 
free  uric  acid  above  o.oi  per  cent,  while  as  a  fact  it  is  present  to  about 
five  times  that  amount,  viz.,  0.05  per  cent.  It  is  probable  that  it  is 
present  in  urine  not  as  free  acid  but  as  salts  of  sodium  or  potassium. 
These  salts  of  uric  acid  are  soluble.  When  acid  fermentation  of  urine 
occurs  the  uric  acid  crystallizes  out  as  a  characteristic  sediment.  It 
is  obtained  from  urine  by  acidifying  when  on  standing  the  uric  acid 
separates  in  more  or  less  colored  crystalline  masses.  It  is  readily 
soluble  in  lithium  carbonate  and  this  compound  is  used  medicinally  for 
dissolving  uric  acid  in  the  form  of  urinary  calculi  which  consist  some- 
times largely  of  uric  acid  and  insoluble  urates.  Uric  acid  reduces 
Fehling's  solution  slightly. 

PHYSIOLOGICAL  RELATIONS  OF  UREA,  URIC  ACID,  ETC. 

Urine  Nitrogen. — The  nitrogen  compounds  which  we  have  been 
discussing,  viz.,  urea,  uric  acid,  creatine  and  creatinine  are  all  present  in 
animal  urine.  The  nitrogen  present  in  all  of  these  substances  comes 
from  protein  material.  They  are  the  waste  or  excretion  products  of 
body  and  food  protein.  When  the  protein  of  the  animal  cells  is  oxidized 
by  means  of  the  oxygen  in  the  blood,  whereby  energy  is  produced,  the 
nitrogen  of  the  protein  thus  oxidized  is  converted  ultimately  into  one  of 
the  compounds  named.  As  these  compounds  are  themselves  oxidiz- 
able,  not  all  of  the  energy  of  the  protein  substance  is  liberated  by  the 
oxidation  in  the  cell.  These  urea  compounds  are  not,  however,  further 
oxidized  in  the  body  but  are  conveyed  by  the  blood  to  the  kidneys 
from  which  they  are  eliminated  in  the  urine  as  excretion  products. 
These  are  not  the  only  nitrogenous  constituents  of  urine  but  they  con- 
stitute by  far  the  larger  proportion  of  the  total  nitrogen  compounds 
present.  In  mammalian  animals  urea  is  the  predominating  nitro- 
genous substance  and  it  is  present  sometimes  in  an  amount  equal  to 
over  90  per  cent  of  the  total  metabolized  protein  nitrogen.  This 
proportion  varies  with  the  total  metabolized  protein  nitrogen  excreted, 
for  when  the  total  nitrogen  is  reduced  the  proportion  of  that  nitrogen 
eliminated  as  urea  is  decreased  to  60  per  cent  and  in  pathological 
cases  has  fallen  as  low  as  14  per  cent.  The  amount  of  urine  excreted 


URIC  ACID  447 

per  day  by  the  average  man  (American)  is  1000-1 200  cc.  In  this 
urine  about  16  grams  of  metabolized  nitrogen  are  present  and  of  this 
16  grams,  14  grams  are  present  as  urea,  and  0.6  gram  as  uric  acid, 
i.o  gram  as  creatinine  and  creatine,  0.7  gram  as  ammonia  and 
0.004  gram  as  other  organic  nitrogen  compounds  known  as  purine 
bases  which  we  shall  next  consider. 

Urine  nitrogen  Urea  14.0    g. 

per  day  =  about  16  g.  Uric  acid          0.6 

in  1000-1200  cc.  Creatinine  1 

urine  Creatine     J 

Ammonia 
.-•*•  '  Purine  bases 


16.304 

This  amount  of  nitrogen  represents  approximately  100  grams  of  protein 
which  is  the  average  amount  of  protein  food  metabolized  per  day. 

Urine  Analysis. — The  determination  of  the  amounts  of  these  nitro- 
genous compounds  in  urine,  especially  of  urea  and  uric  acid,  is  impor- 
tant in  physiological  investigations.  The  quantitative  determination 
of  urea  is  accomplished  by  some  form  of  sodium  hypobromite  de- 
composition, as  already  discussed  (p.  435).  The  uric  acid  is  best 
determined  by  converting  it  into  the  insoluble  ammonium  urate, 
separating  it  as  such,  converting  the  ammonium  urate  into  uric  acid 
by  means  of  sulphuric  acid  and  titrating  the  uric  acid  with  potassium 
permanganate. 

In  urine  two  other  substances  which  do  not  contain  nitrogen  are  of 
especial  importance  as  pathological  constituents. 

Sugar  and  Albumin  in  Urine. — Sugar  (glucose)  occurs  in  urine  in 
the  case  of  the  disease  known  as  diabetes  mellitus.  The  qualitative  test 
and  quantitative  determination  of  glucose  by  means  of  Fehling's 
solution  (p.  332)  are  the  methods  usually  employed.  Normal  urine 
gives  no  glucose  test  with  Fehling's  solution.  Uric  acid  interferes 
slightly  with  this  test  as  it  does  reduce  Fehling's  solution  to  some  extent. 

Albumin. — The  presence  of  albumin  (protein)  in  urine  is  also  patho- 
logic. It  is  tested  for  most  easily  by  what  is  known  as  Heller's  ring 
test.  About  2-5  cc.  urine  are  introduced  into  a  narrow  or  conical  test 
glass.  An  equal  volume  of  concentrated  nitric  acid  is  then  carefully 


448  ORGANIC  CHEMISTRY 

introduced  beneath  the  urine  by  means  of  a  pipette.  On  standing  a 
cloudy  ring  appears  at  the  zone  between  the  two  liquids  in  case  albumin 
is  present. 

D.  PURINE  BASES 

A  group  of  very  interesting  naturally  occurring  compounds  are 
known  which  are  nitrogenous  basic  substances  and  which  are  related  to 
uric  acid.  They  are: 

Caffein 

or  from  coffee  or  tea 

Theine 

Theobromine  from  cacao 
Xanthine  from  urine 
Guanine  from  guano 

From  his  work  on  uric  acid  Fischer  was  led  to  study  these  bases.  He 
showed  that  they  are  directly  related  to  uric  acid  and  the  proof  of 
their  constitution  cleared  up  the  whole  question  in  regard  to  uric  acid. 
It  will  be  unnecessary  here  to  go  into  detail  in  regard  to  the  various 
syntheses  and  reactions  by  which  this  relationship  was  established. 
Suffice  it  to  give  the  conclusions. 

Purine. — Fischer  found  that  all  five  compounds  were  related  to  a 
carbon,  hydrogen,  nitrogen  substance  which  he  prepared  and  called 
purine.  It  was  shown  to  be 


C— HNV 

II  >CH 

N— C N 

Purine 

Xanthine  was  shown  to  be  a  di-hydroxy  purine. 

C(OH)  /NH— CO 


HOC  C— HN  or    OC<  C— HK 

II  \ 

^ 
NH— C N' 

Di-hydroxy  purine,  Xanthine 


PURINE   BASES  449 

Uric  acid  is  tri-hydroxy  purine. 

N  =  C(OH)  /NH—  CO 

HOC/  C— HNV  or    OCX  C— ] 


HN> 


x>co 

N—  C— NT  XNH— C— I 

Tri-hydroxy  purine,  Uric  acid 

Theobromine  was  shown  to  be  di-methyl  xanthine  or  di-methyl 
di-hydroxy  purine. 

7,NH CO 


OG<  C—  N(CH3) 

C 


—  C— 

Di-methyl  di-hydroxy  purine,  Theobromine 

Caffeine  and  theine  were  shown  to  be  tri-methyl  xanthine  or  tri- 
methyl  di-hydroxy  purine. 

/N(CH3)-CO 


OC<  C— N(CH3) 

'CH 


3)—  C— 

Tri-methyl  di-hydroxy  purine,  Caffeine,  Theine 

Guanine  is  the  mono-amino  or  mono-imino  compound  corresponding 
to  xanthine,  i.e.,  imino  xanthine  or  mono-amino  mono-hydroxy  purine. 

/N  =  C(OH)  NH—  CO 

H2N—  C  C—  HN  or    HN  =  C  C—  HN 


N—  C  -  N  NH—  C  -  N 

Imino  xanthine,  Guanine 

Guanine,  therefore,  would  yield  guanidine  as  well  as  urea  (p.  439)- 

The  assigning  of  the  two  types  of  formulas  in  some  cases,  i.e., 

the   hydroxyl  or   alcohol  formula    (enol  formula)  and  the  ketone  or 

carbonyl  formula  (ketone  formula),  is  due  to  the  fact,  not  mentioned 

in  the  case  of  uric  acid,  that  it  is  probably  a  tautomeric  compound 

29 


450  ORGANIC  CHEMISTRY 

existing  sometimes  in  one  form  and  sometimes  in  the  other.  The 
hydroxyl  formula  for  xanthine  seems  to  be'  excluded  by  the  fact  that 
in  it  only  one  imino  hydrogen  remains,  whereas  three  methyl  groups 
may  be  introduced  in  forming  caffeine,  the  tri-methyl  xanthine.  In 
the  ketone  or  carbonyl  formula  three  such  imino  hydrogens  remain. 
Other  nitrogen  bases,  also  shown  to  be  purine  derivatives,  have  been 
discovered,  e.g.,  hypoxanthine,  adenine,  theophylline.  All  of  these 
purine  compounds  will  be  referred  to  again  under  alkaloids  (Pt.  II), 
for  they  really  belong  in  that  group.  Their  relation  to  urea,  however, 
has  made  it  desirable  to  discuss  them  at  this  time. 


PART   II 
CYCLIC  SERIES 


PART  II 
CYCLIC  SERIES 

INTRODUCTION 
RESUME  OF  ALIPHATIC  SERIES 

We  come  now  in  our  study  to  a  very  distinct  and  very  remarkable 
division.  All  of  the  compounds  which  we  have  thus  far  considered 
belong  to  what  we  have  termed  the  aliphatic  series  and  are  genetically 
related  to  methane,  the  simplest  representative.  They  possess  certain 
similar  properties  and  are  represented  by  constitutional  formulas  which 
are  characteristic  of  the  entire  series.  The  compounds  which  we  are 
now  to  study,  and  which  are  related  to  a  hydrocarbon  known  as  benzene, 
exhibit  certain  fundamental  properties  which  are  distinctly  different 
from  those  characterizing  the  members  of  the  aliphatic  series,  and  they 
are  represented  by  constitutional  formulas  of  a  distinctly  different 
character.  It  is  customary,  therefore,  to  classify  organic  compounds 
into  two  large  divisions,  making  the  separation  at  this  point. 

It  must  not  be  inferred,  however,  that  we  shall  find  nothing  in  com- 
mon in  the  compounds  of  the  two  divisions.  Just  as  there  is  no  sharp 
line  of  separation  between  the  two  classes  of  compounds,  inorganic 
and  organic,  so,  we  shall  find,  there  is  no  hard  and  fast  line  separating 
the  divisions  we  are  now  making.  Certain  transition  compounds 
serve  as  a  link  between  the  two,  and  the  compounds  of  this  new  group 
may  also  be  truly  considered  as  genetically  derived  from  methane. 
Also,  we  shall  find  among  these  new  compounds  representatives  of  such 
groups  as  alcohols,  aldehydes,  acids,  etc.,  and  as  such  they  possess  the 
properties  chracteristic  of  these  groups.  It  may  thus  be  considered  as  a 
question  whether  the  similarities  between  the  two  sets  of  compounds 
are  not  of  more  fundamental  importance  than  the  distinctive  differences 
and  whether  it  is  not  more  desirable  to  consider  them  all  together  than 
to  make  the  usual  division.  However,  for  the  purpose  of  teaching  it 
seems  far  better  to  adhere  to  the  classification  commonly  adopted. 

It  will  be  well  before  taking  up  this  new  series  of  compounds  to 

453 


454  ORGANIC  CHEMISTRY 

glance  briefly  at  certain  prominent  characteristics  of  the  aliphatic 
series  in  order  to  emphasize  those  points  which  are  distinctive,  espe- 
cially such  as  have  to  do  with  our  ideas  of  constitution. 

The  paraffin  or  aliphatic  series  of  hydrocarbons  and  their  derivatives 
possess  constitutions  represented  by  structural  formulas  in  which  the 
carbon  atoms  are  linked  together  in  an  open  chain  formation.  For  the 
hydrocarbons  themselves  such  structural  formulas,  written  on  a  plane 
surface,  may  be  illustrated  as  follows : 

H  H    H  H    H    H 

I  I  III 

H— C— H  H— C— C— H  H— C— C— C— H 

H  H    H  H    H    H 

CH4  C2H-6  C3Hg 

Methane  Ethane  Propane 

The  derivatives  of  these  hydrocarbons  result  from  the  substitution 
of  some  monovalent  or  polyvalent  element  or  group  of  elements  in 
place  of  one  or  more  hydrogen  atoms.  Such  compounds  may  be  illus- 
trated by  the  following: 

H  H    H    H  H    H  OH 

I  III  II  I 

H— C— Cl      H— C— C— C— H      H— C— C  =  O      H— C  =  O 

H  H    OHH  H 

CH3— Cl  C3Hr-OH  CH3— CHO       H— COOH 

Methyl  chloride  Iso-propyl  alcohol  Acet  aldehyde  Formic  acid 

Propan-ol-2  Ethan-al  Methanoic  acid 

While  the  chain  of  carbon  atoms  may  become  more  or  less  branched 
it  always  remains  an  open  chain.  Examples  of  straight  and  branched 
chains  may  be  given  by  two  of  the  isomeric  pentanes. 

CH3 

I 
CH3— CH2— CH2— CH2— CH3        CH3— C— CH3 

I 
CH3 

CsHi2  CsHi2 

Normal  pentane  Tertiary  pentane 

2-2-Di-methyl  propane 


INTRODUCTION    TO    CYCLIC    SERIES  455 

All  of  these  examples  are  compounds  which  belong  to  what  are  termed 
the  saturated  series.  In  the  unsaturated  series  the  compounds  also 
have  a  constitution  represented  by  formulas  of  this  same  open  chain 
character;  but,  in  them,  one  or  more  pairs  of  carbon  atoms  are  doubly 
or  triply  linked,  as  follows: 

CH2  =  CH2,  Ethylene  or  Ethene,  C2H4 

CH3— CH  =  CH2,  Propylene  or  Propene,  C3H6 

CH  =  CH,  Acetylene  or  Ethine,  C2H2 

CH3— C  =  CH,  Allylene  or  Propine,  C3H4 

HC  =  C— CH2— CH2— -C  =  CH,  Di-propargyl,  i-5-hexa  di-ine,  C6H6 

The  derivatives  of  these  unsaturated  hydrocarbons  are  wholly  analo- 
gous to  those  of  the  saturated  series,  and  differ  from  them,  in  structure, 
only  as  the  hydrocarbons  themselves  differ,  viz.,  in  the  double  or  triple 
linkage  of  some  of  the  carbon  atoms.  In  each  group  of  similar  hydro- 
carbons, and  also  in  the  derivatives  of  each  group,  we  have  a  more  or 
less  numerous  series  of  compounds  each  member  of  which  differs  from 
its  predecessor  in  the  series  by  a  certain  constant  increase  in  the  number 
of  carbon  and  hydrogen  atoms,  viz.,  by  CH2.  Such  series  are  known  as 
homologous  series  and  may  be  represented  by  general  formulas,  illus- 
trated in  the  case  of  hydrocarbons  themselves,  as  follows : 

Saturated  Hydrocarbons,  CnH2n+2 

Ethylene  Unsaturated  Hydrocarbons,  CnH2n 
Acetylene  Unsaturated  Hydrocarbons,  CnH2n_2 
Dipropargyl  CnH2n_6 

The  relationships  between  these  different  series  have  been  definitely 
established  by  means  of  reactions  which  enable  us  to  pass  from  one 
series  to  another.  Such  reactions  bring  out  a  very  important  fact :  that 
the  hydrocarbons  of  the  unsaturated  series  differ  from  those  of  the 
saturated  series  in  a  very  definite  way,  viz.,  in  the  formation  of  addition 
products.  These  addition  products,  most  readily  formed  with  the 
halogens  or  halogen-hydro  acids,  are  always  the  result  of  the  addition  of 
two ,  four,  or  six  monovalent  atoms  to  each  unsaturated  molecule,  with 
the  conversion  of  the  unsaturated  compound  into  a  saturated  one. 

CH2  =  CH2  +  Br2         >         CH2Br— CH2Br 

Ethylene  Ethylene  bromide 

Di-brom  ethane 


456  ORGANIC  CHEMISTRY 

RING  COMPOUNDS  OF  THE  ALIPHATIC  SERIES 

The  above  relationship  between  saturated  and  unsaturated  com- 
pounds shows  that  they  all  belong  to  the  open  chain  series,  aliphatic 
compounds  or  open  chain  compounds. 

This  holds  rigidly  true  with  the  hydrocarbons  and  their  simpler 
derivatives.  In  the  case  of  certain  derivatives  which  contain  an  an- 
hydride group  a  different  condition  is  sometimes  met  with  in  which  the 
ends  of  the  chain  are  joined  and  what  was  an  open  chain  is  converted 
into  a  closed  chain  or  ring  or  cycle.  The  simplest  case  of  this  nature  is 
the  formation  of  lactones  from  gamma-hydroxy  acids  by  loss  of  water 
(p.  242).  It  will  be  recalled  that  whenever  an  hydroxy  or  an  amino 
acid  which  contains  at  least  four  carbon  groups,  with  the  hydroxy  or 
amino  group  in  the  gamma  or  delta  position,  loses  water  the  first  carbon 
is  brought  into  union  with  the  fourth  or  fifth  carbon  through  the  oxygen 
atom  or  the  NH  group  and  a  ring  is  thereby  formed,  gamma-hydroxy 
butyric  acid  yielding  butyro  lactone  as  follows: 

CH2— CH2— CH2— CO  CH2— CH2— CH2— CO 

i  i  —  M — Url 


O(H  OH) 


O 


•y-Hydroxy  butyric  acid  Butyro  lactone 

gamma-Amino  butyric  acid  yields  pyrrolidon,  CH2 — CH2 — CH2 — CO 


NH 

(p.  851). 

Similarly  delta-amino  valeric  yields  valero  lactam  or  piperidon 

(p.  851). 

CH2— CH2— CH2— CH2— CO 
i  i  —  M — (JJti 

NH(H  OH) 

8  -Amino  valeric  acid 

CH2— CH2— CH2— CH2— CO 


NH 


Valero  lactam,  Piperidon 

Another  well  known  case  is  that  of  the  formation  of  succinic  anhy- 
dride from  succinic  acid,  and  of  succinimide  from  succinamic  acid 

(p.  280,  283). 


INTRODUCTION   TO   CYCLIC   SERIES 


457 


OC— CH2— CH2— CO 

I  I 

0(H  OH) 

CH2— COO(H) 
CH2— CO(OH) 

Succinic  acid 

CH2— CONH(H) 

! 

CH2— CO(OH) 

Succinamlc  acid 


-H— OH 

or 
-H— OH 

-H— OH 


OC— CH2— CH2— CO 
O 


CH2— CO, 
I  > 

CH2— CCK 

Succinic  anhydride 

CH2— CO, 


CH2— 

Succinimide 


NH 


The  ureids  and  uric  acid  have  also  been  explained  by  structural 
formulas  of  this  ring  type  as  follows: 


,NH— CH2 


XNH— CO 

Glycolyl  ureid 
Hydantoin 


, 
OC/ 


Malonyl  ureid 
Barbituric  acid 


NH— CO 


OC 


C— NH 


)co 


NH— C— NH 

Uric  acid 

The"relationship  of  all  of  these  compounds  to  definite  open  chain 
compounds  has  been  thoroughly  established,  and  the  conversion  of  an 
open  chain  into  a  closed  chain  or  ring  is  well  understood.  The  formation 
of  the  ring  results  from  the  linking  together,  through  an  intervening 
non-carbon  element  or  group,  of  the  carbons  which  are  at  the  ends  of  the 
chain  or  which  are  separated  from  each  other  by  at  least  three  interven- 
ing carbons  or  other  groups.  The  uniting  element  or  group  in  the 
compounds  mentioned  is  either  oxygen  or  the  imide  group,  i.e.,  an 
anhydride  grouping,  formed  by  the  loss  of  water  (H2O),  or  ammonia 
(NH3).  Sulphur  also  acts  as  a  link  in  similar  ring  compounds  to  be 
studied  later. 


458  ORGANIC  CHEMISTRY 

Hetero-cyclic  Compounds. — In  no  case,  thus  far  cited,  has  a  ring 
been  formed  which  contains  carbon  groups  only.  Because  of  this 
fact,  that  the  rings  contain  both  carbon  and  non-carbon  groups,  they 
are  termed  heterogeneous  rings  and  the  compounds  are  known  as  hetero- 
cyclic  compounds.  While  the  hetero-cyclic  compounds  which  we  have 
given  as  illustrations  are  directly  related  to  aliphatic  or  open  chain 
compounds,  and  have  been  discussed  in  their  proper  place  as  members 
of  the  aliphatic  series,  there  are  other  hetero-cyclic  compounds  which  are 
either  directly  related  to  benzene  or  which  can  not  well  be  considered 
until  later.  Therefore  the  hetero-cyclic  compounds  as  a  group  will 
constitute  the  last  main  sub-division  or  section  of  our  study. 

We  must,  however,  again  recognize  the  fact  that  while  it  may  seem 
natural  to  classify  organic  compounds  so  that  all  of  those  which  have  an 
open  chain  structure  are  in  one  class,  and  all  of  those  which  have  a  ring 
or  cyclic  structure  are  in  another,  yet  no  such  exact  separation  or 
classification  is  practically  possible. 

Carbo-cyclic  Compounds. — Contrasted  with  the  hetero-cyclic  com- 
pounds, which  we  have  just  been  discussing  in  a  general  way,  we  have 
other  compounds  whose  constitution  is  also  that  of  a  closed  ring  or 
cycle,  but  this  ring  is  composed  of  carbon  groups  only.  To  such  we 
assign  the  names  carlo-cyclic  compounds  or  iso-cyclic  compounds  and 
they  embrace  not  only  hydrocarbons  but  also  all  of  the  different  groups 
of  derivatives  which  we  have  heretofore  studied. 

Benzene. — By  far  the  most  important  and  most  numerous  of  these 
carbo-cyclic  compounds  have  as  their  mother  substance  the  hydrocar- 
bon benzene,  and  the  names  Benzene  Series,  Benzene  Compounds,  or 
Benzene  Derivatives  are  commonly  used  as  synonymous  with  carbo- 
cyclic  compounds.1  This  has  led  to  the  usual  classification  of  organic 

1  It  is  well  to  be  careful  at  the  beginning  in  regard  to  this  word  benzene.  Un- 
fortunately there  is  another  substance  which  goes  commercially  by  the  name 
of  benzine,  and  the  English  language  does  not  allow  of  a  distinction  in  pro- 
nounciation.  The  two  substances  are  wholly  different.  Benzene  is  a  definite 
chemical  compound — an  individual  substance — while  benzine  is  a  mixture  of  several 
compounds,  and  is  simply  a  commercial  product.  Benzine  is  obtained  as  a 
distillation  product  of  crude  petroleum,  and  goes  also  by  the  name  of  petroleum 
ether.  The  use  of  the  word  benzol  in  English  is  wholly  inadvisable.  In  chemical 
terminology  ol  means  a  hydroxy  compound,  and  benzene  is  a  hydrocarbon.  The 
word  benzol  is  German  and  not  English.  In  commercial  usage  benzol  has  become 
common  English,  and  is  frequently  used,  but  care  should  be  taken  to  distinguish 
between  commercial  or  trade  language  and  true  English  chemical  words. 


INTRODUCTION    TO   CYCLIC   SERIES  459 

compounds  into  aliphatic  compounds  and  benzene  compounds.  Such  a 
classification  should  be  understood  in  the  light  of  the  explanations  and 
limitations  which  we  have  been  considering.  In  this  text  the  main 
division  and  classification  used  is  as  follows: 

Part  I:  Aliphatic  or  open -chain  compounds;  including  certain 
hetero-cyclic  compounds  directly  related  to  them. 

Part  II:  Carbo-cyclic  compounds;  including  not  only  carbon  ring 
compounds  derived  from  benezene,  iso-cyclic,  but  also  carbon  ring  com- 
pounds not  derived  from  benzene,  all-cyclic;  in  addition  to  these 
the  hetero-cyclic  compounds  as  a  group. 


SECTION  I.     CARBO-CYCLIC  COMPOUNDS 

A.    ALI-CYCLIC  COMPOUNDS  OR  CARBO-CYCLIC 
COMPOUNDS  NOT  DERIVED  FROM  BENZENE. 

I.    SATURATED  ALI-CYCLIC  COMPOUNDS 

The  hydrocarbons  of  the  general  formula  CnH2n,  the  ethylene  series, 
e.g.,  ethylene,  C2H4  or  CH2  =  CH2,  are  unsaturated  compounds  pos- 
sessing the  characteristic  properties  of  such  compounds,  viz.,  the 
property  of  forming  addition  products  particularly  with  the  halogen 
elements.  Another  group  of  hydrocarbons  is  known,  however,  the 
members  of  which  possess  the  same  general  formula,  but  they  do  not 
form  addition  products,  and  therefore  are  not  members  of  the  un- 
saturated series.  The  compounds  of  this  kind  which  are  known  are 
those  containing  three,  four,  five  and  six  carbon  atoms  as  follows: 

C3H6  Tri-methylene  or  Cyclo  propane 

C4H8  Tetra-methylene  or  Cyclo  butane 

C5Hio  Penta-methylene  or  Cyclo  pentane 

C6Hi2  Hexa-methylene  or  Cyclo  hexane 

What  are  the  properties  of  these  compounds  and  what  is  their 
structure  which 'can  thus  explain  their  isomerism  with  the  olefines, 
and  the  fact  that  they  are  not  unsaturated  ?  The  simplest  member  of 
the  group,  viz.,  C3H6,  is  known  as  tri-methylene  or  cyclo  propane. 

Tri-methylene,  Cyclo  Propane. — It  is  isomeric  with  propylene  for 
which  the  structure  has  been  shown  to  be  CH3  —  CH  =  CH2.  Now 
propylene  is  related  to  propane  in  that  two  hydrogen  atoms  in  propane 
are  lost  from  two  adjacent  carbon  groups,  the  two  carbons  becoming 
doubly  linked. 

-2H 
CH3— CH2— CH3        >        CH3— CH  =  CH2 

Calls  C3He 

Propane  Propylene 

The  result  is  accomplished  by  the  loss  of  two  bromine  atoms  from 
i-2-di-brom  propane  when  it  is  heated  with  sodium. 

460 


ALI-CYCLIC   COMPOUNDS  461 

-2Br 
CH3— CH— CH2       — -        CH3— CH  =  CH2 

Propylene 

(Br      Br) 

i  -2  -Di-brom  propane 

If  instead  of  i-2-di-brom  propane  we  use  i-3-di-brom  propane  the 
product  is  cyclo  propane. 

-2Br  CH2 

CH2— CH2— CH2  Jg  —       CH2— CH2— CH2  or         /        \ 

H2C CH2 


(Br  Br) 

i  -3  -Di-brom  propane  Tri-methylene  or  Cyclopropane 

That  is,  instead  of  two  adjacent  carbons  becoming  doubly  linked  as  in 
propylene,  the  two  end  carbons  become  linked  together  and  the  open 
chain  compound  is  converted  into  a  closed  chain  or  ring  exactly  as  in 
the  lactones  and  lactams.  The  ring,  however,  has  no  intervening  an- 
hydride oxygen  or  NH  group  by  which  the  end  carbons  are  linked,  but 
these  are  linked  directly,  thus  giving  a  carbo-cyclic  not  a  hetero-cyclic 
compound.  The  structural  formula  as  given  above  agrees  with  the 
fact  that  tri-methylene  is  not  an  unsaturated  compound  though  it  has 
the  general  composition  of  the  ethylene  series.  All  of  the  valencies  of 
the  carbons  are  satisfied  and  there  is  no  opportunity  for  the  formation 
of  addition  products.  As  the  compound  contains  three  methylene 
groups  it  is  known  as  tri-methylene,  and  as  it  is  related  to  propane  in 
that  the  open  chain  structure  of  the  latter  is  converted  into  a  ring  or 
cycle  it  is  known  also  as  cyclo  propane. 

What  we  have  said  in  regard  to  the  compound  C3H6  applies  to  the 
others  mentioned,  viz.,  C4H8,  C5Hi0  and  C6Hi2,  which  are  the  members 
of  the  homologous  series.  They  are  each  prepared  from  the  corre- 
sponding saturated  homologue  by  reactions  analogous  to  those  given 
for  tri-methylene.  The  structural  formulas,  as  usually  written,  are  : 

CH2 
H2C-CH,  H20-CH2 


H2C—  CH,  H2C     CH2 

\/  H2C  CH 


L  J 


C4H8  C6Hio  C6H,2 

Tetra-methylene  Penta-methylene  Hexa-methylene 

Cyclo  butane  Cyclo  pentane  Cyclo.hexane 


462  ORGANIC  CHEMISTRY 

Poly-methyl  enes,  Cyclo  Paraffins.— The  names  tetra-methylene  or 
cyclo  butane,  hexa-methylene  or  cyclo  hexane,  etc.,  are  analogous  to 
tri-methlyene  or  cyclo  propane.  For  the  homologous  series  the  names 
poly-methylenes  or  cyclo  paraffins  are  used. 

Ali-cyclic  Compounds. — Cyclo  propane  and  its  homologues,  there- 
fore, are  saturated  carbo-cyclic  compounds.  They  are  similar  to  aliphatic 
compounds  in  certain  respects,  and  are  not  like  benzene  compounds. 
We  indicate  this  by  the  name  ali-cyclic,  as  suggested  by  Bamberger, 
to  distinguish  them  from  the  carbo-cyclic  compounds  related  to  benzene 
which  are  termed  iso-cyclic. 

2.  UNSATURATED  ALI-CYCLIC  COMPOUNDS 

Another  group  of  ali-cyclic  compounds  should  be  mentioned  briefly, 
viz.,  those  which  contain  unsaturated  groups,  i.e.,  carbon  atoms  linked 
by  double  or  triple  bonds.  Just  as  i-3-di-brom  propane  yields  cyclo 
propane  or  tri-methylene  so  i-3-di-brom  propene  yields  a  cyclic  com- 
pound in  which  a  double  bond  is  present. 

CHo— CH  =  CH   i^~2Br          CH2— CH  =  CHor 

I  I  I 


CH-     CH 


(Br  Br)  Cyclo  propene,  CsH4 

i-3-Di-brom  propene 

Compounds  containing  a  triple  linking  are  also  known  and  are  prepared 
by  similar  reactions. 

CH2 

Cyclo  propine,  CaH2 

All  of  these  ali-cyclic  compounds  containing  double  or  triple  bonds  are 
unsaturated  compounds  distinctly  different  from  the  saturated  ali- 
cyclic  compounds. 

Strain  Theory  of  Carbo-cyclic  Compounds 

Referring  again  to  the  saturated  ali-cyclic,  or  poly-methylene,  com- 
pounds and  comparing  them  with  the  isomeric  olefine  compounds,  we 
find  some  exceedingly  interesting  facts.  In  connection  with  the  idea 


ALI-CYCLIC   COMPOUNDS  463 

that  carbon  is  a  tetravalent  element,  and  that  in  organic  compounds 
it  may  best  be  represented  in  space  as  situated  at  the  center pf  a  regular 
tetrahedron,  with  its  four  lines  of  affinity  or  valence  equilaterally  and 
equiangularly  distributed,  we  find  that  the  conversion  of  an  open 
chain  compound  into  a  closed  chain  or  ring  compound  brings  out  some 
very  important  points  which  agree  with  known  facts,  and  which  lead 
to  the  explanation  of  important  relationships.  As  was  explained  in 
connection  with  the  olefine  hydrocarbons,  the  double  bond  existing 
between  two  carbon  atoms  is  a  point  of  weakness  rather  than  strength. 
This  is  indicated  by  the  fact  that  compounds  containing  such  doubly 
or  triply  linked  carbon  atoms  readily  break  one  of  the  double  bonds,  and 
form  addition  products  which  are  saturated  compounds.  The  probable 
explanation  of  this  weakness  is,  that  according  to  the  tetrahedral  or 
space  formulas,  when  two  carbon  atoms  are  doubly  or  triply  linked  the 
lines  of  affinity  or  union  are  subject  to  a  considerable  strain,  while  two 
carbon  atoms  singly  linked  are  under  no  strain.  This  will  be  seen  from 
the  following  drawings  and  still  better  if  the  tetrahedral  models  are 
examined. 


Ethane 
H3c-CK3 


PIG.  7, 


If  now,  by  the  reactions  which  we  have  discussed,  we  convert 
derivatives  of  the  saturated  open  chain  compounds  into  carbo-cyclic 
compounds,  a  strain  is  produced  in  the  formation  of  the  ring  just  as 
there  is  in  the  formation  of  ethylene. 

The  poly-methylene  compounds  may  be  represented  by  the  follow- 
ing drawings: 


464 


ORGANIC  CHEMISTRY 


Trt-methvjlene 

fjH6 
a4*    44' 


Penta-melhyUne 
CsH,. 
0°    44' 


\ 


/" 

,H 


9°44' 


•H 

Hexa-methulene 

CYHu 
-5*    16' 


FIG.  8. 

According  to  the  tetrahedral  theory  the  four  valencies  of  carbon  are 
represented  by  the  four  axes  of  the  regular  tetrahedron.  The  angle 
between  any  two  of  these  axes  amounts  to  109°  28'.  In  the  above 
drawings  the  light  dotted  lines  represent  this  normal  angular  difference 
between  two  of  the  carbon  valencies.  The  heavy  full  lines  linking  the 
carbons  together  show  the  position  which  these  axes  or  lines  of  union 
must  assume  in  the  formation  of  a  symmetrical  cyclic  compound  of 
three,  four,  five  or  six  carbons.  The  amount  in  degrees  and  minutes 
which  is  given  with  each  formula  is  the  angular  distance  through  which 
each  of  the  linking  bonds  must  be  moved  from  the  normal  in  order  to 
form  a  symmetrical  cycle  of  the  carbons.  This  angular  distance 
represents  the  strain  under  which  the  cyclic  compound  exists.  It 
will  be  noticed  that  the  strain  decreases  as  we  pass  from  tri-methylene 
to  tetra-methylene  and  to  penta-methylene  and  that  it  then  increases, 
but  in  the  opposite  direction,  as  we  pass  to  hexa-methylene.  In  the 
case  of  penta-methylene  this  angular  difference  is  so  small  that  it  can 
not  be  shown  in  the  drawing  and  therefore  only  one  set  of  lines 
appears. 

From  these  figures,  which  are  the  result  of  mathematical  calcula- 
tion, we  see  that  the  carbo-cyclic  compounds  which  should  be  the  most 


ALI-CYCLIC   COMPOUNDS  465 

stable  are  those  containing  five  carbon  atoms  in  the  ring,  as  in  penta- 
methylene,  in  which  the  strain  amounts  to  only  o°  44'.  This  is  found 
to  be  the  fact  for  penta-methylene  is  more  stable  than  hexa-methylene, 
tetra-methylene  or  tri-methylene.  It  may  be  mentioned  also  that 
ali-cyclic  compounds  of  more  than  eight  carbons  in  the  ring  have  never 
been  prepared. 

While,  however,  penta-methylene  is  the  most  stable  ali-cyclic  com- 
pound of  the  poly-methylene  group  it  is  hexa-methylene  which  is  of 
special  interest  and  importance.  This  importance  is  due  to  the  fact 
that  it  is  the  connecting  link  between  the  ali-cyclic  compounds  (carbo- 
cyclic  compounds  not  derived  from  benzene,  i.e.,  the  poly  methylenes) 
and  benzene  itself.  Thus  it  becomes  the  connecting  link  between  the 
aliphatic  open-chain  compounds  and  the  very  large  and  important 
division  including  benzene  and  its  derivatives. 


B.  CARBO-CYCLIC  COMPOUNDS  DERIVED  FROM 

BENZENE,  ISO-CYCLIC  COMPOUNDS  OR 

AROMATIC  COMPOUNDS 

i.     BENZENE  SERIES 

A.    HYDROCARBONS 
CONSTITUTION  OF  BENZENE 

Aromatic  Compounds.— The  carbo-cyclic  compounds  which  in 
number  far  exceed  those  of  the  aliphatic  series  were  originally  called 
aromatic  compounds  because  many  of  them  possess  aromatic  proper- 
ties, e.g.,  oil  of  wintergreen,  oil  of  bitter  almonds,  etc.  They  were 
included  with  the  paraffin  compounds  in  the  various  groups  of 
alcohols,  aldehydes,  acids,  etc.  Later  it  was  found  that  they  differed 
from  the  aliphatic  compounds  and  finally  it  was  shown  that  the 
hydrocarbon  benzene  is  related  to  the  aromatic  compounds  just  as 
methane  is  to  the  aliphatic  compounds,  i.e.,  as  the  mother  substance. 

Benzene  Series. — This  gave  rise  to  the  use  of  the  names  benzene 
series  and  benzene  compounds  in  place  of  the  name  aromatic  compounds. 
As  many  of  the  compounds  since  discovered  and  belonging  to  this  series 
are  not  aromatic  the  former  names  are  better  as  all  of  them  are  related 
to  benzene.  Strictly  speaking,  however,  the  benzene  series  proper  does 
not  include  all  of  the  carbo-cyclic  compounds  related  to  benzene  and 
which  are  included  in  the  terms  iso-cyclic  or  aromatic  as  distinct  from 
aliphatic,  e.g.,  naphthalene,  etc.  Generally  speaking,  however,  the 
names  are  used  synonymously. 

Benzene. — What  then  is  benzene,  the  mother  substance  of  this 
large  division  of  organic  compounds  which  as  we  shall  find  are  un- 
surpassed in  their  application  to  the  industries  and  to  daily  life?  When 
coal  gas  is  made  by  the  destructive  distillation  of  coal  the  products 
in  the  first  place  are  probably  water,  methane  and  ammonia.  These 
being  subjected  to  considerable  heat  result  in  the  formation  of  numerous 
more  complicated  compounds.  The  gaseous  products,  consisting  of 
methane,  hydrogen,  etc.,  constitute  crude  illuminating  gas.  The  solid 

466 


BENZENE  SERIES — HYDROCARBONS  467 

residue  is  coke.  The  liquid  products  consist  of  two  parts:  water,  con- 
taining principally  ammonia  gas  in  solution,  and  a  thick  tarry  liquid 
known  as  coal  tar,  which  separates  largely  from  the  water. 

Coal  Tar. — This  coal  tar  is  the  crude  source  of  many  compounds 
of  the  benzene  series.  On  redistillation  of  the  coal  tar  numerous  frac- 
tional distillates  are  obtained  from  which  different  compound  are 
isolated,  (p.  497). 

Light  Oil. — The  first  distillate  which  comes  over  below  170°  is 
known  as  light  oil,  because  it  floats  on  water.  Most  of  the  benzene 
itself  is  obtained  by  further  fractionation  of  this  light  oil. 

CeH6,  CnH2n-6« — By  analysis  and  molecular  weight  determination 
the  formula  for  benzene  has  been  shown  to  be  C6H6.  What  are  the 
properties  of  this  compound  and  how  may  its  structural  formula  be 
represented?  The  formula  C6H6  corresponds  to  the  general  formula 
CnH2n-6  which  would  indicate  an  unsaturated  hydrocarbon. 

Di-propargyl. — Now  we  have  previously  described  an  unsaturated 
hydrocarbon  of  this  composition,  viz.,  di-propargyl  or  i-5-hexa-di- 
ine  (p.  163).  It  was  shown  to  be  a  derivative  of  hexane  containing 
two  triple  bonds  or  acetylene  groups.  The  structural  formula  as 
indicated  by  its  systematic  name  is: 

CH  =  C— CH2— CH2— C  =  CH,    or    C6H6,    i-5-Hexa-di-ine 

Benzene,  however,  is  an  entirely  different  compound  than  this,  i.e.,  it  is 
isomeric  with  di-propargyl.  It  does  not  act  like  an  unsaturated  com- 
pound and,  therefore,  can  not  be  represented  by  a  structural  formula 
like  the  above.  Some  of  the  characteristic  differences  between  these 
two  isomeric  compounds  are  shown  by  the  following  reactions. 

Like  other  unsaturated  compounds  di-propargyl  readily  forms  addi- 
tion products  taking  up  eight  atoms  of  bromine  or  four  molecules  of 
hydrobromic  acid  being  converted  thereby  into  bromine  substitution 
products  of  the  saturated  hydrocarbon  hexane. 

C6H6    +    8Br >        C6H6Br8 

i-5-Hexa-  Octa-brom  hexane 

di-ine 

C6H6    +    4HBr       — >         C6H10Br4 

Tetra-brom  hexane 

Benzene  and  Bromine. — Benzene,  however,  does  not  act  in  this 
way  with  bromine  nor  at  all  with  hydrobromic  acid.  When  bromine 
acts  on  benzene  the  product  usually  formed  is  a  substitution  product, 


468  ORGANIC  CHEMISTRY 

e.g.,  monobrom  benzene  in  which  a  hydrogen  is  substituted  by 
bromine. 

C6H6  +  Br2        --  >        C6H5Br  +  HBr 

Ben-  Mono-brom 

zene  benzene 

If,  however,  the  reaction  'takes  place  in  the  sunlight  an  addition  product 

is  formed;  but,  instead  of  eight  bromine  atoms  being  added,  as  in  the 

case  of  hexa-di-ine,  only  six  bromine  atoms  are  taken  up  by  the  benzene. 

C6H6  +  6Br    --  >        C6H6Br6 

Ben-  Benzene  hexa  -bromide 

zene 

According-  to  our  ideas  of  saturation  this  compound  is  still  unsaturated 
as  it  corresponds  to  the  general  formula  of  the  olefines,  viz.,  CnH2n. 
This  hexa-brom  addition  product  of  benzene  does  not  act  like  an 
unsaturated  compound.  In  contrast  to  such  properties  it  readily 
decomposes  losing  3HBr,  and  becomes  converted  into  a  tri-brom 
substitution  product  of  benzene. 


Benzene  hexa-bromide  Tri-brom  benzene 

Hexa-hydro  Benzene.  —  Similar  to  the  bromine  addition  product  is 
the  hydrogen  addition  product.  Six  hydrogen  atoms  can  be  added  to 
benzene,  but  only  six  as  in  the  case  of  bromine. 

CeHe     +     6H         -  >         C6H12 

Benzene  Hexa-hydro  benzene 

Cyclo-hexane.  —  The  resulting  compound  C6Hi2  corresponds  to  the 
olefine  unsaturated  hydrocarbons,  CnH2n,  and  is  isomeric  with  hexene. 
Hexene,  however,  readily  adds  two  atoms  of  hydrogen  and  yields 
hexane,  whereas  hexa-hydro  benzene  is  with  difficulty  converted  into 
hexane.  The*compound,  therefore,  is  not  unsaturated.  More  im- 
portant still  is  the  fact  that  it  proves  to  be  identical  with  hexa-methy- 
lene  or  cyclo-hexane  which,  as  we  have  recently  shown,  is  a  carbo- 
cyclic  compound  represented  as  follows: 

H2 
C 

H2C 
H2c 


BENZENE  SERIES — HYDROCARBONS  469 

Thus  the  addition  product  formed  by  adding  six  hydrogens  to  benzene 
is  a  compound  which  we  represent  as  six  methylene  groups  linked 
together  in  a  ring. 

Hexagon  Formula. — If  in  hexa-methylene  the  six  methylene  groups 
are  symmetrically  arranged  we  shall  have  a  structural  formula  repre- 
sented by  a  hexagon,  as  this  geometric  figure  is  symmetrical  and  of 
six  points  and  six  sides.  This  has  been  already  shown  on  page  464. 

The  relationship  between  benzene  and  cyclo-hexane  may,  there- 
fore, be  represented  as  follows: 

H2  H 

C  C 

/\  ./\ 

TT  rV^  ^iPTT  ATJ  TT/~*r  ^r'TJ 

xi2^r  i\^xi2  — oxl.  n.v/1  iLxXi 

CH 

C  C 

H2  H 

Cyclo-hexane  Benzene 

Such  a  formula  as  this  agrees  with  the  facts  we  have  thus  far  given  in 
regard  to  benzene,  viz.,  that  it  is  not  an  unsaturated  open  chain  com- 
pound, nor  is  it  an  ali-cyclic  compound  like  cyclo-hexane.  It  is,  how- 
ever, directly  related  to  the  latter. 

Properties. — What  are  other  properties  of  this  compound  benzene, 
and  how  can  its  constitution  be  explained  in  accord  with  these  properties, 
and  does  the  formula  just  suggested,  because  of  its.  relationship  to 
cyclo-hexane,  fit  the  case? 

In  the  first  place,  as  already  stated,  when  benzene  is  treated  with 
bromine,  substitution  products  are  more  readily  formed  than  addition 
products,  and  the  former  are  the  stable  compounds.  While  methane, 
because  of  its  saturated  character,  does  not  form  addition  products, 
but  only  substitution  products,  benzene  forms  both,  but  the  substitu- 
tion products  are  the  more  stable.  Evidently  benzene  is  more  like 
a  saturated  compound  than  an  unsaturated  one  in  spite  of  the  fact 
that  it  has  eight  less  hydrogen  atoms  than  are  sufficient  to  satisfy 
the  six  carbon  atoms  according  to  the  open-chain  structure,  and  six 
less  than  sufficient  according  to  the  cyclo-paraffin  structure. 


470  ORGANIC  CHEMISTRY 

Substitution  Products.— The  substitution  products  of  benzene,  as 
will  be  explained  again  later  on,  are  wholly  analogous  to  those  of  the 
paraffin  hydrocarbons,  and  may  be  simply  illustrated  as  follows : 

C6H5 — Cl,  Mono-chlor-benzene 

C6H4  =  Br2,  Di-brom  -benzene 

C6H5 — OH,  Hydroxy  benzene 

C6H5 — NH2,  Amino  benzene 

C6H5— CH3,  Methyl  benzene 

The  last  compound,  viz.,  methyl  benzene,  is  the  first  of  the  homologous 
series  of  benzene  hydrocarbons  just  as  methyl  methane  is  the  first 
homologue  above  methane. 

Considering  now  benzene  and  its  relation  to  these  substitution 
products  we  find  certain  facts  which  differentiate  it  from  the  paraffin 
hydrocarbons,  and  which  also  enable  us  to  devise  a  satisfactory  struc- 
tural formula. 

Nitro  Products. — (a)  Benzene  and  its  homologous  hydrocarbons 
readily  form  nitro- substitution  products  when  treated  with  nitric  acid, 
whereas  the  paraffin  hydrocarbons  form  nitro-substitution  products 
only  indirectly,  C6H5 — NO2,  nitro  benzene. 

Sulphonic  Acids. — (b)  The  same  is  true  in  regard  to  the  reaction  of 
the  benzene  hydrocarbons  with  sulphuric  acid.  Substitution  products 
are  formed  directly,  and  are  known  as  sulphonic  acids,  C6H5 — SO2OH, 
benzene  sulphonic  acid. 

Homologues  Oxidized. — (c)  The  homologues  of  benzene,  e.g., 
methyl  benzene  or  toluene,  C6H5 — CH3,  are  very  easily  oxidized,  and 
the  methyl  group,  CH3,  is  converted  into  the  carboxyl  group,  COOH. 
This  reaction  takes  place  with  difficulty  in  the  case  of  the  paraffins. 

+0 
C6H5— CH3  — >        C6H5— COOH 

Toluene  Benzoic  acid 

Halogen  Products. — (d)  The  halogen  substitution  products  of 
benzene  are  less  active  than  the  corresponding  products  in  the  paraffin 
series. 

Hydroxyl  Products. — (e)  The  hydroxyl  substitution  products  of 
the  benzene  hydrocarbons  are  more  strongly  acid  than  the  hydroxy 
paraffins,  i.e.,  the  alcohols.  This  means  that  the  radical  (C6H5 — )  is 
more  acid  than  the  radical  (CHa — ). 


BENZENE   SERIES — HYDROCARBONS  471 

Thus  we  see  that  in  these  several  ways  the  benzene  hydrocarbons 
differ  from  their  aliphatic  relatives.  The  preceding  facts  together 
with  those  regarding  isomerism,  which  we  shall  now  discuss,  show  the 
most  striking  properties  of  the  benzene  compounds,  and  when  con- 
sidered in  connection  with  the  relationship  of  benzene  to  cyclo  hexane, 
lead  to  the  most  probable  theory  in  regard  to  the  structure  of  benzene 
itself  and  of  all  of  its  derivatives. 

Isomerism 

A  study  of  the  isomeric  substitution  products  of  benzene  reveals 
some  striking  facts  which  furnish  the  strongest  support  for  the  accepted 
structural  formula. 

One  Mono -substitution  Product. — If  benzene  were  an  open  chain 
unsaturated  compound  similar  to  i-5-hexa-di-ine  we  should  have,  as 
in  the  case  of  the  latter  and  other  like  compounds,  several  isomeric 
mono-substitution  products.  But  benzene  yields  only  one  mono-sub- 
stitution product  of  any  type.  This  can  mean  only  one  thing,  viz., 
that  in  benzene  all  six  ofjheji^drogen  atoms_qre_qfjj&^.. 

Symmetryof  Benzene. — If  then  benzene  is  a  carbo-cyclic  compound, 
as  is  so  strongly  indicated  by  its  relationship  to  cyclo-hexane,  the  struc- 
tural formula  should  express  first  of  all  this  equivalence  or  likeness  of 
the  hydrogen  atoms.  In  any  geometric  representation  of  such  a  con- 
dition we  would  naturally  indicate  it  by  a  symmetrical  figure. 

Hexagon  Formula. — The  hexagonal  arrangement  of  six  carbon 
atoms,  each  one  of  which  holds  in  combination  one  hydrogen  atom, 
gives  us  such  a  symmetrical  structure  for  a  compound  whose  compo- 
sition is  C6H6.  Represented  in  its  simplest  form  and  as  indicated  by 
its  relation  to  cyclo-hexane  we  have 

H 
C 


O 


Benzene 
HC 


C 
H 


472 


ORGANIC  CHEMISTRY 


In  this  formula  all  of  the  hydrogen  atoms  are  represented  as  similarly 
placed  in  reference  to  each  other.  Before  enlarging  upon  this  formula 
and  showing  its  complete  form  let  us  see  if  it  agrees  with  the  facts  in 
regard  to  isomerism.  Its  agreement  with  the  fact  that  only  one  mono- 
substitution  product  is  known  has  just  been  considered.  How  is  it  in 
regard  to  the  poly-substitution  products?  The  facts  are  these: 

.  Three  Isomeric  Di-substitution  Products. — There  are  known  three 
and  only  three  isomeric  di- substitution  products  of  benzene  and  also 
three  and  only  three  isomeric  tri- substitution  products.  All  of  the  three 
possible  isomeric  compounds  are  definitely  known  in  so  many  cases 
that  the  above  statement  is  considered  as  universally  true. 

Three  Isomeric  Tri-substitution  Products. — If  we  examine  the 
hexagon  formula  we  find  that  three  and  only  three  isomeric  substitution 
products  are  possible  in  both  instances,  where  two  and  where  three 
substituting  elements  are  present.  As  in  the  hexagon  formula  all  of 
the  hydrogens  are  alike,  the  only  different  arrangements  conceivable 
for  two  substituting  elements  or  groups  are  the  following: 


X 

c 


X 

c 


X 

c 


HC 


HC 


CX 


CH         HCLs 


OCX        HCL5 


3JCH 


C 
H 

1-2 ;  ortho- 


C 
H 

1-3;  meta- 


4 

SX" 

C 
X 

1-4;  para- 


The  difference  in  these  compounds  must  be  due  to  the  relative  positions 
of  the  two  carbon  groups  in  which  the  substitution  has  occurred. 

Ortho. — Any  compound  formed  by  the  substitution  of  two  elements 
in  any  two  positions  that  are  next  to  each  other  must  be  exactly  the 
same.  That  is,  the  positions  1-2,  1-6,  2-3,  3-4,  4-5,  5-6  are  all  alike 
because  of  the  symmetry  of  our  formula,  and  the  likeness  of  all  of  the 
hydrogen  atoms.  Such  a  compound  is  known  as  an  ortho  compound. 

Meta. — In  the  same  way  positions  1-3,  1-5,  2-4,  2-6,  3-5,  4-6  are 
all  alike  and  only  one  di-substitution  product  is  possible  where  the 
substitution  is  in  carbon  groups  separated  from  each  other  by  one  inter- 
vening carbon.  A  compound  of  this  type  is  known  as  a  meta  compound. 


BENZENE    SERIES — HYDROCARBONS  473 

Para. — Finally  the  third  arrangement  is  the  only  new  form  conceiv- 
able as  positions  1-4,  2-5,  3-6  are  all  alike.  In  this  type  the  substi- 
tuting groups  are  removed  from  each  other  by  two  intervening  carbons, 
or  they  are  directly  opposite  each  other  in  the  hexagon  ring.  Such  a 
compound  is  known  as  a  para  compound.  Therefore  the  possibilities 
of  the  theory  of  the  hexagonal  formula  for  benzene  are  that  three  and 
only  three  di-substitution  products  of  benzene  are  conceivable,  and  this 
is  in  agreement  with  the  fact  that  three  and  only  three  are  known. 

With  the  same  clearness  we  can  show  that  three  and  only  three  tri- 
substitution  products  of  benzene  being  known,  is  in  agreement  with 
our  theory  by  which  three  and  only  three  are  possible.  The  possible 
isomeric  tri-substitution  products  are  shown  as  follows: 

Vicinal,  Unsymmetrical,  Symmetrical. 

X  •  X  X 

c  c  c 

~TT/~*  ^^     ^^>.  /"'"v          trr^1  ^^^     ^>^>^/~'~tr          ur^  .^^     ^^^^. 

-Tlv^p  ^v^^V  XXv^j^  ^VxJjL  Xlvx^ 

HcL  JcX        Hcl  JcX        XcL  . 

C  C  C 

H  X  H 

1-2-3;  1-3-4;  i-3-5; 

vicinal-  unsymmetrical-  symmetrical- 

Examination  will  confirm  the  statement  that  these  three  are  the  only 
different  arrangements  possible  for  1-2-3,  1-6-5  and  2-3-4  are  alike; 
1-3-4,  1-5-4,  1-2-4  and  2-3-5  are  alike;  1-3-5  and  2-4-6  are  alike, 
and  any  x)ther  arrangement  that  can  be  figured  out  will  prove  to  be 
identical  with  one  of  these  three.  Therefore  here  again  the  theory  is 
in  agreement  with  the  facts.  Not  only  then  is  there  agreement  between 
theory  and  fact  in  regard  to  the  relationship  of  benzene  to  cyclo-hexane, 
but  there  is  like  agreement  in  fact  and  theory  in  connection  with 
isomerism  in  the  case  of  poly-substitution  products  and  absence  of 
isomerism  in  mono-substitution  products. 

Position  Isomerism. — This  type  of  isomerism  is  plainly  structural 
isomerism,  but  to  characterize  it  further  it  is  termed  place  or  position 
isomerism. 

Hexagon  Theory  and  Tetra-valence  of  Carbon. — One  point,  how 
ever,  and  that  a  fundamental  one,  we  have  not  yet  considered.  Does 


474  ORGANIC  CHEMISTRY 

the  theory  of  the  hexagon  formula  for  benzene  agree  with  the  tetra- 
valence  of  carbon,  the  idea  so  fundamental  in  connection  with  organic 
compounds?  Plainly,  again,  the  formula  as  we  have  given  it  thus  far 
does  not  agree  with  the  conception  that  carbon  is  tetra-valent,  for  only 
three  valencies  for  each  carbon  are  represented  in  the  formula.  To 
expand  the  simple  hexagonal  formula  to  agree  with  the  idea  of  the 
tetra-valence  of  carbon  it  has  been  necessary  to  introduce  double  bonds 
alternately  into  the  hexagon  ring  formula,  thus  representing  each  car- 
bon with  four  bonds  as  follows: 

H 

C 

^W.r'xj 

Kekule  Benzene 
Formula 


Kekule  Formula. — This  formula,  as  above  represented,  was  devised 
by  August  Kekule  in  1865  and  \  therefore  is  known  and  spoken  of 
as  the  Kekule  Formula  or  the  Kekule  Theory,  also  as. the  hexagon 
formula  and  as  the  benzene  ring. 

Oscillation  Theory. — Careful  consideration,  however,  will  show  that 
the  di-substitution  products  1-2  and  1-6  are  not  exactly  the  same  for 
in  one  case  (1-2)  the  carbon  groups  holding  the  substituting  elements 
are  linked  by  double  bonds,  whereas  in  the  other  case  (1-6)  they  are 
singly  linked.  To  overcome  this  Kekule  claimed  that,  in  such  an 
arrangement  in  space,  oscillation  takes  place  so  that  at  one  instant  the 
structure  is  as  represented,  and  in  the  next  the  double  bonds  change 
position  so  that  the  image  form  of  the  formula  is  in  existence,  oscilla- 
tion from  one  to  the  other  form  taking  place  continually. 

H 
C 


HCr^      ^ICH 

or 
CH         < HCkw        ^PCH 


O 


C 

Benzene  TT 


BENZENE  SERIES — HYDROCARBONS 


475 


Cl 


:O 


CC1 


CH 


C  C 

TT  Di-chlor  benzene  TT 

Facts  that  have  been  brought  to  light  since  the  suggestions  of  Kekule, 
in  the  study  of  tautomerism  and  desmotropism,  give  strong  support  to 
this  oscillation  theory. 

Ladenburg   Formula. — Ladenburg,   however,   not   satisfied  with 
Kekule's  formula  suggested  another  known  as  the  prism  formula. 
CH 


HC 


CH 


CH 

Ladenburg,  Prism  Formula 

Claus,  Armstrong  and  Baeyer. — Still  other  formulas  have  been  sug- 
gested on  account  of  this  difficulty,  each  endeavoring  to  avoid  the 
necessity  of  oscillation  in  order  to  satisfy  the  four  valencies  of  carbon. 
One  of  these  was  suggested  by  Claus  and  called  the  diagonal  formula; 
and  another  by  Armstrong  and  Baeyer  and  known  as  the  centric  formula. 
H  H 

C  C 


HC 


CH 


HC 


Claus,  Diagonal  Formula 
for  Benzene 


Armstrong  andJBaeyer, 
Centric  Formula 
for  Benzene 


476  ORGANIC  CHEMISTRY 

It  is  not  desirable  in  this  place  to  discuss  at  greater  length  these 
other  formulas,  but  simply  to  mention  them  together  with  the  names  of 
the  men  who  have  suggested  them.  All  of  these  men  were  chemists 
who  did  much  to  establish  our  ideas  in  relation  to  the  constitu- 
tion of  benzene  and  its  structural  representation  in  agreement  with 
known  facts.  After  all  of  these  various  suggestions  and  the  discussions 
which  they  brought  forth  Kekule's  original  complete  formula  still 
remains  as  the  best  representation  of  the  structure  of  this  important 
compound,  and  is  the  one  universally  accepted. 

Benzene  Hexagon  in  Space. — One  more  idea  should  be  referred  to 
in  connection  with  the  Kekule  theory.  The  Kekule  formula  as  we 
write  it  represents,  of  course,  no  space  relations,  but  is  simply  a  flat  or 
plane  representation  of  his  idea.  In  accordance  with  the  theory  of 
van't  Hoff  and  LeBel,  carbon  is  represented  as  situated  at  the  center 
of  a  regular  tetrahedron,  and  the  benzene  ring  of  Kekule  becomes, 
therefore,  a  ring  or  hexagon  composed  of  six  such  tetrahedrons.  Such  a 
"formula  will  have  the  space  arrangement  as  given  for  hexa-methylene 
(p.  464).  In  these  poly-methylene  or  cyclo-paraffin  compounds  it 
will  be  recalled  the  penta  and  hexa  carbon  rings  have  the  least  strain, 
the  former  o°  44'  and  the  latter  —5°  16',  and  are  consequently  the  most 
stable. 

After  thus  considering  the  theoretical  basis  for  the  constitution  of 
benzene,  as  it  is  borne  out  by  facts  demonstrated  in  the  laboratory,  we 
shall  now  turn  to  a  consideration  of  the  individual  compounds  of  the 
series  and  their  relation  to  each  other.  We  shall  begin,  as  in  the  ali- 
phatic series,  with  the  hydrocarbons. 

Homologous  Series,  CnH2n_6. — The  homologous  series  of  the 
benzene  hydrocarbons  showing  the  more  important  and  common 
members  is  as  follows : 

C6H6  Benzene. 

C7H8  Toluene. 

C8H10  Xylenes. 

C9Hi2  Mesitylene,  etc. 

CioHu  Cymene,  etc. 

CiiH16  Penta-methyl  benzene,  etc. 

C^His  Hexa-methyl  benzene. 

Ci3H2o  Heptyl  benzene. 

CuH22  Octyl  benzene. 

Ci6H26  Penta-ethyl  benzene. 


BENZENE  SERIES — HYDROCARBONS  477 

Ci8H3o  Hexa-ethyl  benzene. 

C22Hs8  Hexa-decyl  benzene. 

C24H42  Octa-decyl  benzene. 

C26H44  Tri-methyl  hexa-decyl  benzene. 

It  will  be  noted  that  there  are  not  as  many  known  members  of  this 
homologous  series  of  benzene  hydrocarbons  as  there  are  of  the  methane 
series  (p.  19).  There  is  the  same  constant  difference  in  composition 
between  the  successive  members  of  this  series  as  we  found  in  the  case 
of  the  methane  series,  viz.,  CH2,  and  we  shall  find  that  this  is  due  to 
the  same  fact,  viz.,  that  in  converting  any  hydrocarbon  into  the  next 
higher  member  the  methyl  radical  is  substituted  in  place  of  hydrogen. 

Benzene,  C6H6 

Coal  Tar. — Benzene  occurs  in  coal  tar  which  is  a  heavy  liquid  ob- 
tained as  a  distillation  product  when  coal  is  heated  for  the  purpose  of 
making  coal  gas  or  coke. 

It  was  discovered  in  1825  by  Faraday  in  a  liquid  obtained  by  com- 
pressing oil  gas  made  from  shale  or  bituminous  coal,  and  in  1845  Hof- 
mann  found  it  in  coal  tar.  It  is  obtained  from  the  fraction  of  coal  tar 
distillate,  boiling  at  8o°-uo°.  It  boils  at  79°  and  melts  at  5.4°.  Its 
specific  gravity  is  0.90  (o°).  It  is  a  colorless,  light,  mobile  liquid  that 
burns  readily  in  the  air  with  a  smoky  flame  due  to  its  large  amount  of 
carbon. 

Preparation  from  Benzole  Acid. — Benzene  may  be  prepared  from 
its  compounds  by  a  reaction  similar  to  that  used  in  preparing  methane 
from  acetic  acid.  Benzole  acid  bears  the  same  relation  to  benzene 
that  acetic  acid  does  to  methane,  viz.,  a  mono-carboxyl  substitution 
product. 

CH4  CH3— COOH 

Methane  Acetic  acid,  Methanoic  acid 

C6H6  C6H5— COOH 

Benzene  Benzoic  acid 

Benzene  may,  therefore,  be  made  by  distilling  a  mixture  of  benzoic  acid 
and  lime  just  as  methane  is  made  by  distilling  a  mixture  of  acetic  acid 
(or  sodium  acetate)  and  lime. 

2CH3— COONa    +   Ca(OH)2     >     2CH4    +    CaCO3    +  Na2CO3 

Sodium  acetate  Methane 

C6H5— COOH    +    Ca(OH)2    >    C6H6    +    CaCO3    +    H2O 

Benzoic  acid  Benzene 


478  ORGANIC  CHEMISTRY 

Synthesis  of  Benzene  and  Homologues.  —  There  are  other  methods 
of  preparing  benzene  and  its  homologues  which  show  their  relation  to 
the  aliphatic  series.  We  have  already  dwelt  upon  the  relationship 
between  benzene  and  cyclo-hexane,  showing  that  benzene  is  dehydro- 
genated  cyclo-hexane. 

Benzene  from  Acetylene.  —  Benzene  may  be  prepared  directly  from 
one  of  the  unsaturated  open  chain  compounds,  viz.,  from  acetylene, 
CH  =  CH.  When  this  hydrocarbon  is  passed  through  a  red  hot  tube 
it  is  simply  broken  down  into  its  elements.  If,  however,  it  is  heated 
more  slowly,  it  polymerizes  and  benzene  is  obtained. 
3C2H2  --  >  C6H6 

Acetylene  Benzene 

Such  a  polymerization  may  be  represented  in  the  following  manner  in 
agreement  with  ideas  in  regard  to  both  acetylene  and  benzene. 
CH  CH 


HC  CH  HC  CH 

III  —  II  I 

HC  CH  HC  CH 

/  \      / 

CH  CH 

V:  3C2H2  C6H6 

Acetylene  Benzene 

Mesitylene  from  Allylene.  —  In  a  similar  way  methyl  acetylene  or 
allylene  polymerizes  and  yields  mesitylene  which  is  tri-methyl  benzene. 

CH3  CH3 

C  C 

\  /     V 

HC  CH  HC  CH 

H3C—  C  C—  CH3        H3C—  C  C—  CH3 

/  \     S 

CH  CH 

3CH^C—  CH3  C6H3(CH3)3 

Allylene  Mesitylene 

These  two  syntheses  are  of  especial  importance  as  showing  the  direct 
relationship  between  the  hydrocarbons  of  the  aliphatic  series  and  the 
hydrocarbons  of  the  benzene  series. 


BENZENE    SERIES — HYDROCARBONS 


479 


Toluene,  C&H.&— CH3 

Toluene  occurs  naturally  in  the  balsam  of  tolu,  hence  its  name. 
It  occurs  also  in  coal  tar,  along  with  benzene.  It  is  found  mostly  in 
the  fraction  of  coal  tar  distillate  boiling  at  no°-i4O°. 

Fittig's  Synthesis. — When  Kekule  brought  out  his  benzene  theory 
the  relation  between  toluene  and  benzene,  the  first  two  members  of 
the  homologous  series  of  benzene  hydrocarbons,  was  not  known.  It 
was  worked  out  by  Fittig  and  Tollens  by  means  of  what  is  known  as  the 
Fittig  synthesis,  which  is  based  on  a  reaction  exactly  analogous  to 
the  Wurtz  reaction  for  the  synthesis  of  the  homologous  members  of  the 
aliphatic  series  of  hydrocarbons. 

When  a  halogen  substitution  product  of  benzene,  e.g.  brom  benzene, 
is  treated  with  a  methyl  halide  and  metallic  sodium,  toluene  is  obtained. 
This  proves  that  toluene  is  methyl  benzene. 


Br)CH 


+   2Na  +  Br)CH5 


C6H5— CH3    +    2NaBr 
CHS 


HC 


CH 


Toluene,  Methyl  benzene 

Fittig  first  called  the  product  of  this  reaction  methyl  benzene,  and 
did  not  know  that  it  was  toluene.  When,  however,  the  identity  of 
this  substance  with  toluene  was  proven  it  cleared  up  at  once  the  re- 
lationship between  the  first  two  members  of  the  homologous  series  of 
benzene  hydrocarbons  and  later  of  the  entire  series. 

Friedel-Craft  Reaction. — Another  synthetic  reaction  of  great  im- 
portance in  preparing  the  homologues  of  benzene  is  the  Friedel-Craft 
reaction.  When  a  hydrocarbon  is  treated  with  a  methyl  halide  in  the 
presence  of  aluminium  chloride  the  methyl  group  is  substituted  in  the 
hydrocarbon. 


480  ORGANIC  CHEMISTRY 

C6H5—  (H  +  Br)—  CH3  +  (A1C13)        r->     C6H5—  CH3  +  HBr 

CH 

(H    +    Br)CH3 
C 

+  (A1C13) 

Hc  CH 

C  C 

H  H 

Benzene  Toluene,  Methyl  benzene 

Toluene  is  similar  to  benzene  in  its  general  appearance.  It  is  a 
colorless,  light,  mobile  liquid  boiling  at  110°,  and  with  specific  gravity 
of  0.88  (o°).  In  its  chemical  properties  toluene  is  distinctly  different 
from  benzene. 

Ease  of  Substitution.  —  The  substitution  products  of  toluene  are 
much  more  readily  formed  than  similar  ones  in  the  case  of  benzene. 
The  presence  of  a  methyl  group  substituted  in  the  benzene  ring  seems 
to  make  the  compound  more  easily  susceptible  to  further  substitution 
in  the  ring  itself. 

Oxidation.  —  Oxidizing  agents  which  attack  benzene  with  difficulty 
react  readily  with  toluene,  and  the  substituted  methyl  radical  becomes 
oxidized  to  carboxyl. 

+0 
C6H6—  CH3  ---  '    C6H5—  COOH 

Toluene  Benzole  acid 

This  oxidation  of  the  methyl  radical  to  carboxyl  emphasizes  a  differ- 
ence between  benzene  compounds  and  aliphatic  compounds  for  in  the 
latter,  it  will  be  recalled,  the  direct  oxidation  of  a  methyl  group  to  a 
carboxyl  group  is  impossible.  Only  one  toluene  is  known  which  agrees 
with  the  theory  as  only  one  mono-methyl  benzene  is  possible. 

/CH3 
Xylenes,  CeH 


Isomeric  Xylenes.  —  Xylene  has  been  shown  to  have  the  constitu- 
tion of  di-methyl  benzene,  but  as  we  should  expect,  being  a  di-sub- 
stituted  benzene  three  isomeric  hydrocarbons  are  known  all  of  which 


BENZENE    SERIES  —  HYDROCARBONS  481 

have  this  constitution.     This  constitution  has  been  proven  by  means  of 
Fittig's  synthesis  from  di-brom  benzene  and  from  brom  toluene. 

,(Br       2Na       Br)—  CH3  /CH, 

+  +  —  >     C6H/  +4NaBr 


(Br       2Na       Br)—  CH3 

Di-brom  benzene  Xyiene,  Di-methyl  benzene 


C6H  +  2Na  +  Br)—  CH3  -  —  >  C6H  +  2NaBr 

\Br  \CH3 

Brom  toluene  Xyiene,  Di-methyl  benzene 

Ethyl  Benzene.  —  By  the  same  synthesis  another  hydrocarbon  has 
been  made  from  mono-brom  benzene  and  ethyl  bromide  which  has 
the  empirical  formula  CsHio,  but  which  must  be  mono-ethyl  benzene. 

C6H5—  (Br  +  2Na  +  Br)—  C2H5    -  >     C6H5—  C2H5  +  2NaBr 

Brom  benzene  Ethyl  benzene 

These  two  compounds  di-methyl  benzene  and  mono  -ethyl  benzene 
are  simple  structural  isomers,  while  the  three  di-methyl  benzenes  are 
place  isomers. 

These  hydrocarbons  together  with  toluene  clearly  illustrate  the 
fact  that  the  homologous  members  of  the  benzene  series  of  hydrocar- 
bons bear  exactly  the  same  relationship  to  each  other  as  do  the  homolo- 
gous members  of  the  aliphatic  series  of  hydrocarbons.  The  homology 
in  both  cases  is  due  to  the  same  fact,  viz.,  that  the  methyl  radical  is 
substituted  for  a  hydrogen  of  a  hydrocarbon  in  making  the  homologous 
hydrocarbon  next  higher  up,  i.e.  containing  one  more  carbon  atom. 
The  composition  of  the  homologues  changes  by  the  quantity  CH2. 


CH3—  H  CH3—  CH3  CH3—  CH2—  CH3 

Methane  Ethane  Propane 


I 

C6H6— H  •         C6H5— CH3  C6H4<f 

Benzene  Toluene  ^PTT 

Mono-methyl  benzene  L,±l3 

Xylenes 
Di-methyl 
benzenes 

and 

C6H5— (CH2— CH3) 

Mono-ethyl  benzene 
31 


482 


ORGANIC  CHEMISTRY 


The  three  di-methyl  benzenes  are  known  as  the  xylenes,  and  the  mono- 
ethyl  benzene  simply  as  ethyl  benzene. 

Orientation. — According  to  our  theory  the  three  known  xylenes  or 
di-methyl  benzenes  being  di-substitution  products  must  be  represented 
by  the  three  isomeric  formulas  due  to  the  position  of  the  substitution 
groups  in  the  benzene  ring  as  explained  on  p.  472.  These  are  as 
follows: 


CH 


H 


m 

c 

H 

ortho-Xylene 


CH3 

C 

C— CH3     HCr^^N 

CH  HcL  Jc— CH3     HC 

.       C 
H 

meta-Xylene 


CH 


L  J 


CH3 

para-Xylene 


CH 
CH 


As  the  three  compounds  are  definite  individuals  possessing  different 
properties  such  as  melting  point,  boiling  point,  specific  gravity,  etc., 
the  question  now  is,  to  which  of  these  compounds  do  we  give  one  formula 
and  to  which  another?  In  other  words,  which  one  of  the  xylenes  is  the 
ortho  compound,  which  is  the  meta  and  which  the  para?  Without 
taking  the  matter  up  in  its  historical  connection  as  to  whether  these 
names  were  first  given  to  definite  compounds,  and  the  positions  then 
determined;  or  whether  they  were  first  given  to  the  definite  positions 
and  the  compounds  then  named  accordingly;  we  can  simply  state  now, 
for  the  purpose  of  the  following  explanation,  that  the  compound  with 
the  two  substituting  groups  in  the  1-2  positions  is  the  ortho  compound; 
the  one  with  the  1-3  positions  is  the  meta  and  the  1-4  is  the  para. 

Ortho -meta-  and  para-Xylenes. — The  three  definite  isomeric 
xylenes  have  the  following  physical  properties  which  enable  us  to 
distinguish  them  from  each  other.  For  the  present  we  may  designate 
them  simply  as  A,  B,  C. 

Xylene  A  has  m.p.  —28°;  b.p.  142°;  sp.  gr.  0.893 
Xylene  B  has  m.p.  —53°;  b.p.  139°;  sp.  gr.  0.881 
Xylene  C  has  m.p.  +13°;  b.p.  138°;  sp.  gr.  0.880 


BENZENE   SERIES  —  HYDROCARBONS  483 

If  we  examine  the  formulas  of  the  three  isomers,  we  find  that  if  in  each 
one  we  substitute  a  third  element  or  group  in  the  benzene  ring, 
each  one  of  the  original  di-substitution  products  possess  different  pos- 
sibilities as  to  the  number  of  isomeric  products  that  can  be  formed. 
Taking  first  the  simplest  case,  we  find  for  the  1-4  di-methyl  benzene, 
that  all  four  of  the  remaining  positions,  viz.,  2,  3,  5,  6,  bear  exactly  the 
same  relation  to  the  already  substituted  methyl  groups.  It  will  make 
no  difference  then  whether  a  third  group  is  substituted  in  position  2,  3 
5  or  6.  If  the  three  xylenes  are  converted  into  mono-chlor-xylenes  by 
substituting  one  chlorine  atom  into  the  benzene  ring  we  may  expect 
to  find,  that  in  one  case,  only  one  product  is  obtained  no  matter  what 
method  of  preparation  is  used.  This  is  the  fact. 

para-Xylene.  —  The  xylene  which  boils  at  138°  and  melts  at  13° 
and  the  specific  gravity  of  which  is  0.880  yields  only  one  chlor-xylene. 
The  methyl  groups  must,  therefore,  be  in  the  positions  i  and  4,  and 
the  chlorine  may  be  either  2,  3,  5  or  6.  This  xylene  must  be  then  the 
para  compound. 


CH3  CH3 

I  I 

c  c 


CH3  CH3 

para-Xylene  chlor-Xylene 

i  -4  -Di-methyl  benzene  i-4-Di-methyl  (2-,  3-,  5-  or  6) 
M.P.  13°.     B.P.  138°  chlor  benzene 


The  other  two  xylenes  yield  not  one  only  but  more  than  one  isomeric 
mono-chlor  xylene.  One  of  the  xylenes  yields  two  isomeric  products 
while  the  other  one  yields  three. 

ortho  -Xylene.  —  A  similar  examination  of  the  formulas  shows  that 
with  the  i  -2  -di-methyl  benzene  two  isomeric  mono-chlorine  substitu- 
tion products  are  possible. 


484 


ORGANIC  CHEMISTRY 

CH, 


ortho-Xylene 

i-2-Di-methyl 

benzene 


i-2-Di-methyl 
3-chlor  benzene 


i-2-Di-methyl 
4-chlor  benzene 


The  position  6  is  plainly  in  the  same  relation  to  i  and  2  that  3  is, 
and  5  the  same  as  4  so  that  no  other  mono-chlor  xylene  is  possible  if 
the  methyl  groups  are  originally  in  positions  i  and  2.  The  xylene 
which  boils  at  142°  and  melts  at  —28°  is  the  one  which  yields  two 
and  only  two  mono-chlor  substitution  products,  and  it  is,  therefore, 
ortho- xylene. 

meta-Xylene. — The  remaining  isomeric  xylene  must  of  necessity 
be  the  meta  compound,  i.e.  i-3-di-methyl  benzene,  but  we  have  just 
as  conclusive  proof  in  this  case  as  in  the  others.  The  xylene  boiling 
at  139°  and  melting  at  —53°  when  converted  into  the  mono-chlorine 
substitution  product,  with  the  chlorine  in  the  ring,  yields  three  iso- 
meric compounds.  From  a  study  of  the  formulas  it  is  readily  seen,  in 
this  instance  also,  that  the  only  di-methyl  benzene  which  is  possible  of 
conversion  into  three  isomeric  mono-chlor  xylenes  is  the  meta  or  1-3 
compound. 


C— Cl 


C— CH3 


HC 


CH3 


meta-Xylene 

i  -3  -Di-methyl 

benzene 


i  -3  -Di-methyl 
2-chlor  benzene 


BENZENE    SERIES — HYDROCARBONS 
CH,  CH3 


485 


HC 


— CH; 


HC 


C1C 


:— CH3 


i -3 -Di -methyl 
4-chlor  benzene 


C 
H 

i-3-Di-methyl 
5-chlor  benzene 


The  position  6  is  the  same  in  relation  to  the  two  methyl  groups  as  the 
position  4  so  that  no  other  isomer  is  possible.  The  xylene  with  the 
properties  given  is,  therefore,  meta-xylene.  Writing  the  formulas  for 
the  three  xylenes,  with  their  properties,  we  have: 

CH3  CH3  CH3 

I  I  I 


HC 


HC 


o 


C— CH3     HC 


Vx 

o 


CH 


C— CH3     HC 


C 
H 

ortho-Xylene 
i -2 -Di-methyl  benzene 


C 
H 

meta-Xylene 
t  -3 -Di-methyl  benzene 


-53" 

139° 

0.881 


CH3 

para-Xylene 
i -4 -Di-methyl  benzene 

13° 
I380 
0.880 


M.P.  -28° 

B.P.  142° 

Sp.  gr.  0.893 

Having  thus  determined  in  the  case  of  the  three  di-methyl  benzenes 
which  is  the  ortho,  which  the  meta  and  which  the  para  compound,  we 
have  a  shorter  direct  method  for  a  similar  proof  in  the  case  of  any  di- 
substitution  product  of  benzene.  It  becomes  necessary  simply  to 
convert  the  undetermined  compound  into  xylene  and  whichever' xylene 
is  obtained  we  assume,  unless  there  is  proof  of  a  migration  of  one  of  the 
groups,  that  in  the  original  compound  the  two  substituting  groups 
occupied  the  same  positions  as  the  methyl  groups  in  the  resulting  xylene. 
As  the  number  of  di-substitution  products  of  benzene  which  have  been 


486  ORGANIC  CHEMISTRY 

thus  oriented  has  increased,  the  process  becomes  continually  more 
simple,  for  it  is  only  necessary  to  convert  the  unknown  compound  into 
any  one  of  several  known  compounds.  This  method  of  determining 
which  one  of  three  isomeric  di-subtituted  benzenes  is"  the  ortho,  meta  or 
para  compound  was  first  developed  by  Kb'rner,  who  carried  it  out  in 
connection  with  the  di-brom  benzenes.  The  process  is  known  as  Kor- 
ner's  orientation.  A  method  was  also  developed  by  Griess  with  the 
di-amino  benzoic  acids.  Nolting  used  the  above  method  with  the 
three  xylenes  as  we  have  described  it. 

Oxidation  of  Xylene.  —  Just  as  toluene  on  oxidation  has  the  methyl 
group  converted  into  carboxyl  yielding  a  mono-carboxyl  or  mono-basic 
acid,  benzoic  acid,  so  the  xylenes  by  oxidation  yield  di-carboxyl  or 
di-basic  acids  of  the  corresponding  ortho,  meta  or  para  constitution. 
The  two  methyl  groups  are,  moreover,  possible  of  oxidation  one  at  a 
time  so  that  intermediate  mono-carboxyl  or  mono-basic  acids  result  in 
which  one  methyl  group  remains.  The  di-basic  acids  are  known  as 
phthalic  acids  and  the  mono-basic  acids  as  toluic  acids. 

,CH3  ,CH3  ,COOH 

v  CeH^v  CeH^v 

XCH3  XCOOH  XCOOH 

o-,  m-,  p-Xylene  o-,  m-,  p-ToIuic  o-,  m-,  p-Phthalic 

acids  acids 

Hydrocarbons,  C9Hi2 

Vicinal,  Unsymmetrical,  Symmetrical,  Tri-methyl  Benzenes.  —  As 
was  explained  in  discussing  isomerism  of  the  benzene  substitution 
products  (p.  473)  tri-methyl  benzene  can  exist  in  the  three  forms,  vicinal 
or  1-2-3,  unsymmetrical  or  1-3-4,  symmetrical  or  1-3-5.  All  three  of 
these  are  known  and  they  are: 

Mesitylene,          1-3  -5  -Tri-methyl  benzene,  symmetrical. 
Pseudo-cumene,  1-2  -4  -Tri-methyl  benzene,  unsymmetrical. 
Hemelithene,       1-2  -3  -Tri-methyl  benzene,  vicinal. 
The  proof  that  these  three  compounds  are  all  tri-methyl  benzenes  is 
that  by  oxidation  they  each  yield  first  a  mono-basic  acid,  second  a 
di-basic  acid  and  finally  a  tri-basic  acid. 

COOH 


XCH 


COOH  COOH  COOH 


Tri-methyl  Mono-basic  Di-basic  Tri-basic 

benzene  acid  acid  acid 


BENZENE  SERIES — HYDROCARBONS  487 

How  can  we  prove,  as  in  the  case  of  the  xylenes  or  di-methyl  ben- 
zenes, which  formula  belongs  to  which  compound? 

Mesitylene,  1-3-5-  Tri-methyl  Benzene. — Taking  up  first  mesity- 
lene,  two  reactions  show  that  this  particular  hydrocarbon  must  have 
the  1-3-5  or  symmetrical  constitution. 

Oxidation  of  Mesitylene. — By  oxidation  it  is  converted  into  a 
mono-basic  acid  which  on  being  heated  with  sodium  hydroxide  loses 
CO2  and  yields  one  of  the  di-methyl  bezenes  or  xylenes.  The  par- 
ticular xylene  thus  obtained  is  always  meta-xylene  or  1-3 -di-methyl 
benzene. 

CH3  CH3 

C  C 


H3C 


-cl  Jc—  CH8  H(OOC)—  cl  Jc—  CH3 

C  C 

H  H 

Mesitylene  Mesitylenic  acid 

-3  -5  -Tri-methyl  i-3-Di-methyl 

benzene  5-carboxy  benzene 


CH3 


-C02 
>       HCL  JC— CHS 


L  Jc— 


C 
H 

meta-Xylene 
i -3 -Di-methyl  benzene 

Clearly  the  only  tri-methyl  benzene  that  can  thus  always  yield  1-3 -di- 
methyl benzene  is  the  one  in  which  the  three  methyl  groups  are  in  the 
symmetrical  positions,  the  1-3-5  positions,  so  that  whichever  methyl 
group  is  oxidized  the  remaining  two  will  be  in  the  i  -3  positions.  Fur- 
ther oxidation  of  mesitylene  gives  a  di-basic  acid  which  yields  toluene, 
and  complete  oxidation  of  the  methyl  groups  gives  finally  a  tri-basic 
acid  which  yields  benzene. 


488 


ORGANIC  CHEMISTRY 


CH3 

I 

c 


CH3 

I 
C 


H3C— 


+0 
C— CH3  HOOC— 


C— COOH 


C 
H 

Mesitylene 


C 
H 

Uvitic  acid 


CH; 

I 

C 


-2CO2 


HC 


HC 


CH3 
C 


O 

C 
H 

Toluene 

COOH 


CH 
CH 


H3C— 


:— CH3 


HOOC— ( 


CH 

C— COOH 


C 
H 

Mesitylene 


C 
H 

Tri-mesitic  acid 
H 
C 


HC 


CH 


C 
H 

Benzene 


BENZENE    SERIES — HYDROCARBONS 


489 


Synthesis  of  Mesitylene  from  Allylene.  —  The  second  proof  of  the 
symmetrical  structure  of  mesitylene  is  its  synthesis  from  allylene  and 
also  from  acetone.  The  synthesis  from  allylene  has  already  been 
spoken  of  in  connection  with  the  proofs  of  the  structure  of  benzene 
(p.  478),  and  is  exactly  analogous  to  the  synthesis  of  benzene  by  the 
polymerization  of  acetylene. 

HC  HC 


HC 


HC 


CH 


CH 


polymerization 
by  heat 


\ 


HC 


HC 


CH 


CH 


CH 

Acetylene 

CH3 


CH 

Benzene 

CH3 


HC 


H3C— C 


\ 


CH 
C— CH3 


i         •     »i  HC 

polymerization          1 1 

by  heat    H3C— C 


\ 


CH 
C— CH3 


C 
H 

Allylene,  Methyl  acetylene 


\ 
C 

H 

Mesitylene 

From  Acetone. — By  treating  acetone,  CH3 — CO — CH3,  with  con- 
centrated sulphuric  acid,  water  is  eliminated,  polymerization  takes 
place  similar  to  that  in  the  above  reactions,  and  mesitylene  is  obtained. 
The  reaction  is  represented  as  follows: 

CH3  CH3 


H2)HC 

H3C— C 
(O 


O)  =  C 


\ 


CH(H2 
(O 


/   \ 
—  HO  HC  CH 

polymerization     H3C — C  C — CH3 


C—  CH3 


/ 


H2)H 
Acetone 


H 

Mesitylene 


4QO  ORGANIC  CHEMISTRY 

Substitution  Products  of  Mesitylene.— A  final  proof  of  the  structure 
of  mesitylene  is  the  fact  that  it  yields  only  one  mono-substitution  prod- 
uct, and  only  one  di-substitution  product,  when  the  substitution  takes 
place  in  the  benzene  ring.  This  will  appear  clear  on  examination  with- 
out writing  out  the  formulas.  As  all  three  of  the  unsubstituted  hydro- 
gens of  mesitylene  remaining  in  the  benzene  ring  are  exactly  alike  in 
relation  to  the  methyl  groups  it  can  make  no  difference  which  one  or 
which  two  are  substituted,  the  product  will  be  the  same.  This  condi- 
tion exists  only  in  the  case  of  the  i-3-5-tri-methyl  benzene  and  in 
neither  of  the  other  two,  the  1-2-3  or  tne  I~3~4  compounds. 

Mesitylene  occurs  in  coal  tar  together  with  the  other  hydrocarbons 
we  have  considered.  It  is  a  liquid  resembling  benzene  and  toluene. 
Its  boiling  point  is  165°. 

Pseudo-cumene,  i-2-4-Tri-methyl  Benzene. — The  second  hydro- 
carbon, isomeric  with  mesitylene,  and  therefore  tri-methyl  benzene, 
is  known  as  pseudo-cumene.  It  occurs  also  in  coal  tar,  and  resembles 
mesitylene  in  its  properties.  Its  boiling  point  is  169°.  Its  structure 
is  proven  to  be  1-2-4- tri-methyl  benzene  from  the  following  reactions. 

Pseudo-cumene  from  Brom  para-Xylene  and  Brom  meta-Xylene. 
Bfrom  para-xylene,  as  will  be  recalled  from  the  discussion  of  the  con- 
stitution of  para-xylene,  exists  only  in  one  form  as  no  isomeric  com- 
pounds are  possible.  This  substance,  by  means  of  Fittig's  synthesis, 
yields  pseudo-cumene,  the  constitution  of  which,  therefore,  can  only  be 
i -3 -4- tri-methyl  benzene. 

CH3  CH3 


'C(Br  +2Na  +  Br)CH3    >     HCk  .^C— CH3 

C 

CH3  CH3 

Brom  para-xylene  Pseudo-cumene 

i-4-Di-methyl  1-3 -4 -Tri-methyl 

3 -brom  benzene  benzene 

Brom  meta-xylene  exists  in  three  isomeric  forms  (p.  473)  and  one  of 


BENZENE    SERIES  —  HYDROCARBONS  49  1 

these  only,  viz.,   the   i-3-di-methyl  4-brom  benzene,  yields    pseudo- 
cumene  by  Fittig's  synthesis. 
CH3 


HC  L          Jc—  CH3  Hcl.          y  C—  CH3 

C  C 

(Br  +  2Na  +  Br)CH3  | 

i  -3  -Di-methyl  4-Brom  benzene 


Pseudo-cumene 
i  -3  -4  -Tri  -methyl  benzene 

Hemelithene,  i-2-3-Tri-methyl  Benzene.  —  The  third  isomeric 
tri-methyl  benzene  is  known  as  hemelithene  and  proves  to  be  the 
1-2-3  compound.  It  resembles  the  other  two  isomers,  and  like  them  is 
found  in  coal  tar.  It  boils  at  175°. 

Propyl  and  Iso-propyl  Benzenes.  —  In  addition  to  the  three  tri- 
methyl  benzenes  we  still  have  three  isomeric  hydrocarbons  of  the  com- 
position CgHi2.  These  compounds  are  isomeric,  depending  on  the 
substitution  in  benzene  of  other  radicals  than  methyl.  Substitution  of 
one  propyl  radical  for  one  benzene  hydrogen  atom  gives  us  a  compound 
of  the  same  composition  as  that  obtained  by  substituting  three  methyl 
radicals  for  three  hydrogen  atoms.  As  the  propyl  radical  has  two 
isomeric  forms,  viz.,  that  of  normal  propyl  and  that  of  isopropyl,  so 
we  have  the  two  substitution  products,  propyl  benzene,  C6H6  —  CH2— 

/CH3 
CH2—  CH3,  and  iso-propyl  benzene,  C6H5—  CH<T          •    The  former 

boils  at  159°,  and  the  latter  at  153°.    The  iso-propyl  benzene  is  also 
known  as  cumene.     The  third  compound  isomeric  with  the  tri-methyl 

/CH3 
benzenes  is  methyl  ethyl  benzene,  CeHX  ,  which  exists  in  three 


forms,  o,  m,  and  p. 

Hydrocarbons, 

Durene  and  Cymene.  —  Two  hydrocarbons  of  this  composition  are 
of  importance  because  of  their  close  relation  to  turpentine  and  camphor. 


4Q2  ORGANIC  CHEMISTRY 

Durene  is  the  i-2-4-5-tetra-methyl  benzene.  It  has  a  camphor-like 
odor  and  is  found  in  coal  tar.  It  can  be  made  from  one  of  the  di-brom 
meta-xylenes,  viz.,  the  i-3-di-methyl  4-6-di-brom  benzene  by  Fit- 
tig's  synthesis. 

CH3  CH; 


H3C— 


HCk^          .^C— CH3  HCk.         >C— CH3 

sX^ 

CBr 

i-3-Di-methyl 
4-6-di-brom  benzene 

CH3 

Durene 

1-2-4-5-  (or  1-3-4-6) 
Tetra -methyl  benzene 

Cymene.  i -Methyl  4-Iso-propyl  Benzene. — Cymene,  the  only 
other  isomeric  hydrocarbon  of  the  composition  CioHi4,  which  we  shall 
consider,  is  shown  to  be  i -methyl  4-iso-propyl  benzene,  by  its  synthe- 
sis from  para-brom  toluene  and  isopropyl  bromide. 

CH3  CH3 


Hc  cH  Hc  cH 

C 

I  /CH3 

(Br  +  2Na  +  Br)CH(  CH 

para-Brom  toluene  \r^TJ  /        \. 

i -Methyl  4 -brom  benzene  ^X13  /  \ 

te^/1      H'C  CH3 

Cymene 
i -Methyl  4-iso-propyl  benzene 

Cymene  is  found  in  thyme  oil,  eucalyptus  oil,  and  Roman  cummin 
oil.  It  is  also  obtained  by  heating  camphor  with  phosphorus  pentoxide 
and  from  turpentine  by  reduction  with  iodine. 

Ci0H16+2l    >     C10H14+2HI 

Turpentine  Cymene 


BENZENE   SERIES  —  HYDROCARBONS  493 

These  relationships  will  be  discussed  more  fully  when  we  consider 
turpentine  and  camphor,  and  it  will  be  found  that  these  two  important 
substances  have  the  same  ring  structure  as  cymene.  The  other  hydro- 
carbons of  the  benzene  series  need  not  be  discussed  in  detail.  It  is 
sufficient  to  know  of  their  existence  in  the  homologous  series  as  given 
in  Table  (p.  476). 

Hydrocarbons,  CnH2n-8  and  CnH2n-io 

It  is  best  to  speak  at  this  time  of  hydrocarbons  derived  from  benzene 
by  the  substitution  in  the  ring  of  unsalurated  open  chain  radicals.  Just 
as  the  homologues  of  benzene  are  prepared  by  substitution  of  a  saturated 
paraffin  radical,  methyl,  ethyl,  propyl,  etc.,  in  the  benzene  ring,  so 
other  series  of  hydrocarbons  have  been  obtained  by  substituting 
radicals  of  the  unsaturated  open  chain  hydrocarbons  of  the  ethylene 
and  acetylene  series.  These  new  compounds  will  be  poorer  in  hydrogen 
than  the  benzene  series  by  two  and  four  atoms  respectively. 

Styrene,  Phenyl  Ethylene.  —  The  first  of  these  hydrocarbons  is 
known  as  styrene.  It  is  obtained  from  storax,  a  resin  found  in  the 
plant,  Styrax  officinalis.  It  is  also  present  in  coal  tar.  It  is  related 
to,  and  also  prepared  from,  cinnarnic  acid,  an  important  acid  to  be 
considered  later.  Styrene  is  a  liquid  boiling  at  140°.  Its  constitution 
is  proven  by  its  synthesis  from  benzene  and  ethylene  when  a  mixture 
of  the  two  compounds  is  passed  through  a  red  hot  tube. 

-2H 
C6H5(H  +  H)CH  =  CH2    --  >    C6H5—  CH  =  CH2 


Benzene  Ethylene  Styrene 

Phenyl  ethylene 

The  radical  (CeH5  —  ),  is  known  as  phenyl  and  styrene  is,  therefore, 
phenyl  ethylene,  naming  it  as  a  substitution  product  of  ethylene. 
As  a  benzene  substitution  product  its  name  is  ethylenyl  benzene. 

Phenyl  Propene  or  Propenyl  Benzene.—  While  the  next  higher 
member,  which  is*  phenyl  propene,  C6H5  —  CH2  —  CH  =  CH2,  is  not 
important  in  itself  we  shall  find  later  (p.  623)  that  derivatives  of  it  are 
present  in  some  very  valuable  essential  oils  found  in  plants.  A  case  of 
isomerism  is  present  here  which  it  is  well  to  mention.  Two  compounds 
are  known  both  of  wlych  correspond  to  phenyl  propene,  the  isomerism 
being  due  to  the  position  of  the  double  bond,  or  if  we  look  at  the  com- 
pound as  a  phenyl  substitution  product  of  propene,  it  is  due  to  the  posi- 


494  ORGANIC  CHEMISTRY 

tion  in  which  the  phenyl  group  is  substituted  in  propene.  The  two 
formulas  are  as  follows: 

C6H5— CH2— CH  =  CH2      and      C6H5— CH  =  CH— CH3 

•y-Phenyl  propene  a-Phenyl  propene 

This  is  exactly  analogous  to  the  isomerism  of  the  halogen  propenes 
(p.  164). 

Phenyl  Acetylene. — The  only  other  hydrocarbons  of  this  kind  that 
we  shall  mention  are  phenyl  acetylene,  C6H6 — C  =  CH,  which  is  a 
liquid  boiling  at  140°,  and  a-phenyl  propine,  C6H5C  =  C — CH3. 

These  hydrocarbons  naturally  possess  the  properties  of  both  benzene 
and  unsaturated  open  chain  compounds. 

COAL  TAR 

"Coal  tar;  at  first  a  troublesome  waste  product,  now,  its  derivatives, 
the  host  of  aromatic  compounds,  are  applicable  in  numberless  and  daily 
increasing  ways  in  the  sciences,  arts  and  industries.  They  are  indis- 
pensable as  aids  in  the  hands  of  the  chemist,  the  physiologist,  the 
bacteriologist  and  the  doctor,  and  are  serviceable  in  the  multiform 
needs  of  the  dyeing  industry,  painting,  photography  and  the  manu- 
facture of  explosives.  They  are  the  artificial  dyes,  the  synthetic 
medicines,  the  aroma  of  plants  and  of  the  musk  ox,  food  stuffs  hundreds 
of  times  sweeter  than  sugar,  and  destructive  explosives." 

Thus  speaks  Heinrich  Caro,1  one  of  the  prominent  workers  in  the 
development  of  the  coal  tar  industry  in  Germany. 

All  of  the  hydrocarbons  which  we  have  mentioned,  with  the  excep- 
tion of  phenyl  acetylene,  are  found  in  coal  tar.  In  addition,  other 
hydrocarbons  which  we  shall  consider  later,  and  several  derivatives, 
especially  hydroxyl  and  amino  derivatives,  are  likewise  obtained  from 
it.  It  is,  therefore,  of  great  importance  as  a  source  of  benzene  com- 
pounds, and  a  consideration  of  the  subject  from  a  commercial  stand- 
point is  best  made  now. 

Illuminating  Gas. — A  large  part  of  the  illuminating  gas  used  in  our 
cities  is  made  by  distilling  soft  or  bituminous  coal. 

Distillation  of  Coal. — In  this  process  of  manufacture  the  coal  is 
heated  in  large  iron  or  brick  stills  out  of  contact  with  the  air.  By  such 
a  distillation  the  coal  is  broken  down  into  three  main  groups  of  sub- 
stances, gases,  liquids  and  solids. 

Gaseous  Products. — The  gaseous  product  is  composed  largely  of 
hydrogen,  methane,  carbon  monoxide,  carbon  dioxide,  nitrogen, 
.  25  (c),  955;  1892. 


COAL   TAR 


495 


ammonia  and  hydrogen  sulphide,  with  small  amounts  ofhydro  carbons 
other  than  methane  including  acetylene  and  benzene. 

Liquid  and  Solid  Products.  Coal  Tar. — The  liquid  products  con- 
sist of  water  holding  ammonia  in  solution  and  a  heavy  oil-like  sub- 
stance known  as  coal  tar.  The  solid  residue  left  in  the  retort  is  known 
as  coke,  and  contains  the  unburned  and  uncombined  carbon  together 
with  the  non-volatile  constituents  of  the  coal  representing  the  mineral 
matter  or  ash. 

Methane,  CH4 

Hydrogen,  H2 

Carbon  monoxide,  CO 

Carbon  dioxide,  CO2 
gas       j  Nitrogen,  N2 

Ammonia,  NH3 

Cyanogen,  (CN)2 

Hydrogen  sulphide,  H2S 

Other  hydrocarbons,  C2H2,  C6H6,  CioH8,  etc. 


+heat 
Coal > 


liquid 


Ammoniacal  liquor  (water  +  NH3,  etc.) 
Coal  Tar 


solid     { Coke 

Composition  of  Illuminating  Gas. — The  volatile  liquid  and  gaseous 
products  are  first  led  through  cool  tubes  or  condensers  where  the  liquid 
portion  is  retained.  The  gaseous  product  is  then  washed  with  water, 
and  purified  to  remove  cyanogen,  ammonia,  hydrogen  sulphide  and 
most  of  the  carbon  dioxide.  The  washed  gas,  containing  methane, 
hydrogen,  carbon  monoxide,  some  of  the  carbon  dioxide,  nitrogen  and 
the  miscellaneous  hydrocarbons  in  small  amount,  is  the  illuminating 
gas  as  used. 

Methane,  CH4  36  per  cent 

Hydrogen,  H2  47  per  cent 

Carbon  monoxide,  CO       8  per  cent 

Purified  illuminating  gas.          Nitrogen,  N2  4  per  cent 

Approximate  composition.        Carbon  dioxide,  CO2          i  per  cent 

Acetylene,  C2H2 

Benzene,  C6H6  4  per  cent 

Naphthalene,  CioH8 


496  ORGANIC  CHEMISTRY 

Ammonia. — The  liquid  portion,  held  by  the  condenser,  consists  of 
the  ammoniacal  liquor  (water  solution  of  ammonia  and  some  other 
compounds)  and  coal  tar,  and  is  easily  separated  into  the  two  con- 
stituents. The  ammoniacal  liquor  together  with  the  wash  water  from 
the  purification  of  the  gas  is  known  as  gas  liquor  and  forms  the  large 
commercial  source  of  ammonia  and  ammonium  salts. 

Gas  Liquor  Salt,  Ammonium  Sulphate. — When  this  liquor  is  neu- 
tralized with  sulphuric  acid,  or  if  the  wash  water  contains  sulphuric 
acid,  it  yields  on  evaporation  a  crystalline  mass  known  as  gas  liquor 
salt.  This  salt  is  largely  ammonium  sulphate,  and  is  the  crude 
ammonium  sulphate  used  in  the  fertilizer  industry  as  the  chief  source  of 
ammonia  nitrogen.  The  coal  tar  after  separation  from  the  ammoniacal 
liquor  is  subjected  to  fractional  distillation. 

Coke. — The  solid  non-volatile  residue  or  coke  is  used  as  fuel,  espe- 
cially in  the  iron  and  steel  industry.  Most  of  the  coke  so  used  is  made 
in  coke  ovens  in  which  the  gas  and  liquid  products  were  originally  allowed 
to  escape  into  the  air  and  were  wasted.  In  recent  years  much  of  the 
coal  tar  formerly  wasted  is  now  recovered.  Thus  with  the  develop- 
ment of  our  knowledge  of  the  benzene  series  of  compounds,  which  in- 
clude valuable  dyes,  explosives,  medicines,  etc.,  this  substance  that  was 
formerly  thrown  away  has  become  a  most  important  industrial  prod- 
uct. So  important  are  the  compounds  obtained,  either  directly  or 
indirectly,  from  it  that  the  name  coal  tar  has  become  an  adjective 
of  common  use  and  significance  as  shown  by  the  terms,  coal  tar  in- 
dustry, coal  tar  products,  coal  tar  dyes. 

Chemically  coal  tar  is  a  highly  complex  mixture  of  many  compounds, 
but  fortunately  these  may  be  separated  and  obtained  in  a  pure  condi- 
tion by  fractional  distillation  and  treatment  with  acids  and  alkalies. 
The  detailed  study  of  most  of  these  compounds  will  be  taken  up  later, 
but  before  discussing  their  separation  from  coal  tar  it  will  be  well  to 
describe  their  general  character.  They  belong  to  three  classes,  viz., 
(i)  neutral  compounds  or  hydrocarbons,  (2)  acid  compounds  or  phenols, 
and  (3)  basic  nitrogen  compounds.  The  hydrocarbons  obtained  from 
coal, tar  are  the  ones  we  have  already  studied,  viz.,  benzene,  toluene, 
xylene  and  mesitylene,  and,  in  addition  to  these,  naphthalene,  anthra- 
cene and  phenanthrene  which  are  related  to  benzene  but  belong  to 
other  more  complex  series.  The  acid  compounds  are  known  by  the 
general  name  of  phenols  from  the  simplest  member  phenol  or  carbolic 


COAL   TAR 


497 


acid.  They  are  hydroxyl  substitution  products  of  the  hydrocarbons. 
The  ones  obtained  from  coal  tar  are  phenol,  cresols  or hydroxy  toluenes, 
xylenols  or  hydroxy  xylenes  and  naphthols  or  hydroxy  naphthalenes. 
The  basic  compounds  are  amino  substitution  products  of  the  hydro- 
carbons, viz.,  aniline  or  amino  benzene,  of  which  there  is  only  a 
very  small  amount  present,  and  heterocyclic  nitrogen  bases  known 
as  pyridine  and  quinoline.  The  five  most  important  compounds 
are  benzene,  toluene,  naphthalene,  anthracene  and  phenol  which 
together  are  obtained  in  a  yield  of  10  to  15  per  cent  of  the  coal  tar. 
The  remaining  85  to  90  per  cent  of  the  tar  constitutes  the  residue  left 
after  it  is  distilled.  This  residue  is  known  as  pitch  or  tar  and  is  used  to 
manufacture  some  heavy  oils  used  as  crude  creosote  for  impregnating 
wood  paper,  etc.,  and  as  tar  for  road-making,  etc. 

Fractional  Distillation  of  Coal  Tar. — The  distillation  of  the  coal  tar 
is  carried  out  in  iron  retorts,  and  fractions  distilling  at  certain  tem- 
peratures are  obtained.  These  fractions  vary  somewhat  in  different 
works  and  with  different  tars,  but  the  following  may  be  given  as  a 
general  result. 

FRACTIONAL  DISTILLATION  OF  COAL  TAR 


Product 


Distillation 
temperature 


11. 


III. 


IV. 


V. 


Light  oil  (crude  naphtha) 

(Principally  benzene  hydrocarbons  with  some  phenols, 

some  bases  and  some  naphthalene) 
Middle  oil  (phenol  or  creosote  oil) 

(Principally  phenols,  25  per  cent,  and  naphthalene,  50 

per  cent) 
Heavy  oil 

(Principally  naphthalene  and  anthracene) 
Anthracene  oil : 

(Most  of  the  anthracene) 
Pitch  or  tar. . . 


Below  170°  or  210° 


170   or  210 
to  230°  or  240' 

230°  or  240° 

to  270° 
Above  270° 

Residue 


Fraction  I,  known  as  light  oil  because  it  floats  on  water  (sp.  gr.= 
0.975),  contains  some  ammoniacal  liquor  from  which  it  separates.  The 
separated  oil  contains  mostly  hydrocarbons  of  the  benzene  homologous 
series,  but  there  are  also  present  in  it  some  phenols,  some  basic  com- 
pounds and  some  naphthalene.  The  acid  and  basic  compounds  may 

32 


ORGANIC  CHEMISTRY 


be  removed  at  this  stage  or  after  the  next  fractionation  by  treatment 
with  alkali  and  then  with  acid.  The  alkali  forms  soluble  salts  with 
the  phenols  which  may  then  be  removed  by  washing  with  water;  and 
similarly  the  basic  nitrogen  compounds  are  removed  by  means  of  acid 
and  then  washing  with  water.  The  treated  and  washed  light  oil  is 
then  subjected  to  a  new  fractional  distillation.  The  fractions  usually 
collected  are: 

FRACTIONAL  DISTILLATION  OF  LIGHT  OIL 


Product 

Distillation 
temperature 

4 

90  Per  cent  benzene.  

80°  to  110° 

ft 

(Benzene  with  some  toluene) 
50  Per  cent  benzene 

1  10°  to  140° 

c 

(Toluene  and  xylene  with  some  benzene) 

140°  to  1  70° 

r> 

(Xylene  and  mesitylene) 
Phenol  oil       

I  7O°  to  IQ^° 

F 

(Phenols) 
(Sometimes  combined  with  D)  

Residue 

(Naphthalene) 

90  Per  Cent  Benzene. — Fraction  A  contains  actually  about  70  per 
cent  of  benzene  and  about  30  per  cent  of  toluene.  Commercially  it  is 
known  as  90  per  cent  benzene  because  90  per  cent  of  it  distils  below  100°. 

50  Per  Cent  Benzene. — Fraction  B  contains  about  46  per  cent  of 
benzene,  the  rest  being  toluene  and  some  xylene.  Commercially  it  is 
termed  50  per  cent  benzene  because  50  per  cent  of  it  distils  below  100°. 
Fraction  C  contains  the  higher  hydrocarbons  xylene  and  mesitylene, 
etc.,  and  practically  no  benzene  or  toluene.  If  treatment  with 
alkali  and  acid  has  not  been  previously  carried  out  these  fractions  are 
now  subjected  to  such  treatment  to  remove  phenols  and  basic  com- 
pounds and  are  then  again  fractionated  to  obtain  the  pure  hydrocar- 
bons. Most  of  the  phenols  are  present  in  fraction  D.  This  fraction 
is  often  not  collected  separately,  but  becomes  part  of  the  residue  which 
is  combined  with  the  middle  oil.  The  middle  oil  contains  often  as 
much  as  50  per  cent  of  naphthalene,  which  crystallizes  out  if  the 
oil  is  cooled,  and  is  separated  by  means  of  a  centrifuge.  The  oil 
thrown  off  from  the  centrifuge  yields  a  little  benzene,  toluene  and 


COAL    TAR  499 

xylene  in  a  first  fraction  which  is  mixed  with  fresh  light  oil  and 
fractionated  with  it.  The  second  fraction  from  the  middle  oil  con- 
tains mostly  phenols  with  some  bases  which  are  separated  in  the 
usual  way.  The  third  fraction  will  contain  some  naphthalene  not 
obtained  in  the  first  crystallization.  The  residue  from  the  middle  oil 
contains  some  anthracene  and  is  combined  with  the  heavy  oil.  The 
heavy  oil  which  contains  principally  naphthalene,  about  28  per  cent, 
and  anthracene  but  also  some  phenols,  about  16  per  cent,  is  separated 
into  three  fractions  by  distillation  in  a  vacuum.  The  first  contains  fhe 
phenols,  the  second  the  naphthalene  and  the  residue  contains  principally 
anthracene  which  is  separated  by  means  of  hydraulic  pressure.  The 
final  coal  tar  fraction  or  anthracene  oil  contains  anthracene  and  some 
phenanthrene.  The  latter  is  extracted  by  means  of  petroleum  ether 
as  a  solvent,  and  from  the  residue  the  anthracene  is  separated  by 
pressure. 

In  the  preceding  discussion  of  the  recovery  and  fractional  distillation 
of  coal  tar,  in  the  process  of  coal  gas  manufacture,  we  have  considered 
only  the  direct  cooling  method.  While  this  is  the  method  commonly 
used  heretofore,  the  more  progressive  concerns  are  utilizing  the  principle 
of  fractional  cooling  and  washing  such  as  has  been  devised  by  Feld. 
The  general  process  may  be  briefly  described  as  follows:  Instead  of 
being  cooled  in  one  condenser  to  the  ordinary  temperature  of  water,  15° 
to  20C,  thus  condensing  all  of  the  liquid  products  into  one  tar,  the  vapors 
given  off  by  distilling  the  coal  are  fractionally  cooled  and  washed.  The 
first  cooling  is  only  to  about  160°  to  200°.  This  yields  a  coal  tar  as  in 
the  other  method  but  the  amount  is  necessarily  small.  After  cooling 
to  this  temperature  the  rest  of  the  cooling  is  carried  out  in  a  series  of 
condensers  each  one  a  little  lower  in  temperature  than  the  preceding. 
These  condensers  also  contain  a  washing  liquid  through  which  the 
gas  passes  and  to  which  the  gas  gives  up  certain  of  its  constituents.  In 
the  higher  temperature  condensers  the  wash  liquid  is  successively  heavy 
oil,  middle  oil  and  light  oil.  The  temperature  of  these  condensers 
or  washers  is  about  as  follows:  160°,  80°,  60°,  and  40°.  In  them  most 
of  the  coal  tar  products  are  retained  and  are  later  separated  by  frac- 
tionating the  wash  liquids  with  the  similar  oils  obtained  from  the  coal 
tar.  In  the  next  condensers,  the  temperatures  of  which  run  about  as 
follows:  38°,  34°,  18°,  the  wash  liquid  is  water.  These  water  wash 
liquors  absorb  from  the  gas  practically  all  of  the  ammonia,  hydrogen 


500  ORGANIC  CHEMISTRY 

sulphide,  and  cyanogen  gases  and  also  separate  out  from  the  gas  some 
of  the  benzene  and  naphthalene  which  are  still  in  solution  in  the  gas. 
As  a  result  of  this  fractional  cooling  and  washing  a  part  of  the  coal  tar 
is  at  once  fractionated  and  the  coal  gas  issues  from  the  final  washer 
practically  pure  and  nearly  free  from  tar  constituents.  The  total  yield 
of  tar  products  is  increased  over  that  obtained  by  the  direct  cooling 
process  and  the  amount  of  benzene  and  naphthalene  left  in  the  illumi- 
nating gas  is  diminished  as  much  as  is  practicable  for  a  gas  of  proper 
illuminating  power.  For  details  of  this  process,  which  it  is  not  advis- 
able to  consider  here,  the  student  is  referred  to  technical  works  such 
as  Wagner,  "Coal  Gas  Residuals." 

Yield  from  Coal  Tar. — The  yield  of  coal  tar  in  the  original  disl  il- 
lation of  the  coal  is  about  2  to  5  per  cent,  but  it  depends  upon  many 
physical  or  mechanical  factors  such  as  temperature  and  pressure  of  the 
distillation,  the  form  of  the  still,  the  length  of  time  and  the  tempera- 
ture to  which  the  volatile  products  are  heated,  etc.  Approximate 
yields  from  the  redistillations  of  the  coal  tar  may  be  stated  as  follows : 

Benzene,  toluene  and  xylene i.o-  2.5  per  cent 

Naphthalene 4.0  -10.0  per  cent 

Anthracene o.  25-  2 . o  per  cent 

Coal  tar,      I  Phenol 6.4-0.5  per  cent 

100  per  cent  \  Cresols 2.0-  3.0  per  cent 

Pyridine  and  quinoline 0.2-0.3  Per  cent 

Creosote  oil 25.0  -30 .  o  per  cent 

Pitch  or  tar 50.0  -60.0  per  cent 

Coal  Tar  Industry. — The  importance  of  the  coal  tar  industry  may 
be  gathered  from  consideration  of  a  few  statistics.  Germany  produced, 
in  1890,  100,000  tons  of  coal  tar  from  gas  works  and  60,000  tons  from 
coke  ovens.  England  produced  700,000  tons  of  coal  tar  from  all 
sources.  Thus  England  leads  in  the  production  of  coal  tar.  Germany, 
however,  leads  all  other  countries  in  the  utilization  of  coal  tar,  import- 
ing a  large  part  of  that  produced  elsewhere.  In  1890  Germany  had 
twenty-one  factories  thus  utilizing  coal  tar  and  the  value  of  the  prod- 
ucts made  from  it  amounted  to  $25,000,000.  Since  1914  the  produc- 
tion of  coal  tar  and  its  utilization  in  the  United  States  have  increased 
tremendously.  This  development  has  been  so  rapid  that  accurate 
figures  are  impossible  to  obtain. 


COAL   TAR  501 

Theories  of  Formation  of  Benzene,  etc. — Theories  of  the  forma- 
tion of  these  benzene  products  in  the  distillation  of  coal  have  been 
investigated  principally  by  Berthelot,  and  his  conclusions  are,  in 
general:  In  the  first  place,  coal  decomposes  by  heat  yielding  simple 
paraffin  compounds  such  as  methane,  ethylene,  acetylene,  alcohol, 
acetic  acid,  etc.  These  compounds  when  subjected  to  higher  tempera- 
tures polymerize  into  benzene,  and  the  higher  hydrocarbons  naphtha- 
lene, anthracene,  phenanthrene,  etc.,  and  into  derivatives  of  these 
such  as  phenol,  aniline,  pyridine,  etc. 


B.  DERIVATIVES  OF  BENZENE  HYDROCARBONS 

I.  HALOGEN  DERIVATIVES 

The  derivatives  of  the  benzene  series  of  hydrocarbons  may  be 
grouped  in  very  nearly  the  same  classes  as  the  derivatives  of  the  ali- 
phatic hydrocarbons,  as  follows: 

A.  Halogen derivatives 

B.  Sulphuric  and  sulphurous  acid derivatives 

C.  Nitric  and  nitrous  acid derivatives 

D.  Ammonia derivatives 

E.  Azo  and  other  intermediate  nitrogen derivatives 

F.  Di-azo derivatives 

G.  Ring  hydroxyl derivatives  (Phenols) 

H.  Side  chain  hydroxyl derivatives  (Alcohols) 

I.    Aldehydes  and  ketones 

J.    Acids 

K.  Substituted  acids 

In  considering  these  different  classes  it  will  be  found  that  they 
bear  the  same  relationship  to  the  hydrocarbons  from  which  they  are 
formed  as  do  the  corresponding  derivatives  of  the  aliphatic  series  to 
their  respective  hydrocarbons. 

While  the  general  methods  of  preparation  and  the  "characteristic 
reactions  of  analogous  classes  in  the  two  series  of  derivatives  are 
sometimes  the  same  they  are  more  often  distinctly  different.  The 
halogen  derivatives  of  the  benzene  series  are  not  formed  from  the  hy- 
droxyl derivatives,  as  in  the  aliphatic  series,  but  by  direct  action  of  the 
halogen.  Their  reactions  also  are  different.  The  'sulphuric  acid  and 
nitric  acid  derivatives  which,  in  the  aliphatic  series,  are  formed  with 
difficulty,  and  are  not  generally  important;  in  the  benzene  series  are 
formed  with  ease  and  are  extremely  important  and  very  reactive. 
The  ammonia  derivatives  which,  in  the  aliphatic  series,  are  formed 
from  the  halogen  compounds;  in  the  benzene  series  are  formed  by  re- 
ducing the  nitric  acid  derivatives.  The  azo  and  di-azo  derivatives  of 
the  benzene  series  are  among  the  most  important  compounds  we  shall 

502 


HALOGEN   DERIVATIVES  503 

study ;  whereas  in  the  aliphatic  series  only  a  few  compounds  of  the  class 
are  known.  The  hydroxyl  derivatives  of  the  benzene  series  are  of  two 
distinct  classes ;  one  of  which  includes  true  alcohols  analogous  to  those 
of  the  aliphatic  series,  the  other  includes  compounds  known  as  phe- 
nols, which  are  acid  compounds.  The  aldehydes  and  ketones  of  the 
two  series  are  in  general  formed  by  similar  reactions  and  are  of  similar 
character  though  in  the  benzene  series  a  new  class,  known  as  quinones, 
are  entirely  distinctive.  The  acids  of  the  benzene  series  while  they 
may  be  prepared  by  the  oxidation  of  aldehydes  as  in  the  aliphatic 
series  are  often  prepared  by  the  oxidation  of  a  methyl  group  to 
carboxyl. 

On  the  other  hand,  the  ammoniacal  character  of  the  ammonia  de- 
rivatives, the  alcoholic  character  of  the  true  benzene  alcohols  and  the 
general  reactions  of  aldehydes  and  acids  are  alike  in  the  two  series  of 
derivatives.  What  has  just  been  said  applies  in  most  cases  to  those 
derivatives  of  the  benzene  series  in  which  the  compound  is  formed  by 
substitution  in  the  benzene  ring.  As  we  shall  find  later  the  derivatives 
of  this  series  are  of  two  kinds:  (a)  those  in  which  substitution  is  in 
the  ring,  and  (b)  those  in  which  substitution  is  in  the  side  chain  of  the 
benzene  homologues.  These  latter  compounds  are  wholly  analogous 
to  corresponding  aliphatic  compounds  as  in  the  case  of  the  true  alco- 
hols of  the  benzene  series  just  mentioned.  The  order  of  taking  up  the 
different  classes  varies  in  the  two  series  because  of  the  ease  of  prepara- 
tion and  the  importance  of  the  sulphuric  and  nitric  acid  derivatives 
of  the  benzene  series. 

HALOGEN  BENZENES 

We  speak  of  the  halogen  derivatives  because  in  the  benzene  series 
we  have  both  addition  products  and  substitution  products.  While 
benzene,  as  we  stated  previously,  does  not  act  like  an  unsaturated 
compound  it  does,  nevertheless,  form  relatively  unstable  addition  prod- 
ucts though  with  more  difficulty  than  substitution  products.  The 
addition  products  of  the  unsaturated  hydrocarbons  of  the  paraffin 
series  are  very  easily  formed  and  are  stable  compounds;  in  fact  are 
identical  with  substitution  products  of  the  saturated  series. 

CH2  + 2Br    >     CH2Br— CH2Br 

Ethylene  Ethylene  bromide  or 

Di-brom  ethane 


504 


ORGANIC  CHEMISTRY 


Hexa-hydro   Benzene. — With  hydrogen  benzene  forms   a  hexa- 
hydro  addition  product  which  is  hexa-methylene  or  cyclo-hexane. 


H 
C 


H2 
C 


Benzene 


H'CO 

H2ck^J 


Hexa-hydro 

benzene 

Hexa-methylene 
Cyclo  hexane 


C 
H 


C 

H2 


Benzene  Hexa-chloride. — When  chlorine  acts  upon  benzene  in  the 
sunlight  benzene  hexa-chloride  is  formed  which  is  unstable  readily 
losing  3HC1,  yielding  tri-chlor  benzene,  a  stable  tri-chlor  substitution 
product. 


H 
C 


HC1 
C 


HC 
HC 


o 


H 

Benzene 


+  6C1 


C1HC 
C1HC 


-3HC1 


CHC1 


HC1 

Benzene  hexa-chloride 


Cl 
C 


HC 


HC 


C 

Cl 

Tri-chlor  benzene 


Halogen  Substitution  Products. — When,  however,  chlorine  acts  on 
benzene  in  diffused  light,  substitution  products  are  formed  directly. 
This  takes  place  more  readily  in  the  presence  of  halogen  carriers,  e.g. 
ferric  chloride,  FeCl3;  aluminium  bromide,  AlBr3;  antimony  chloride, 


HALOGEN   DERIVATIVES  505 

SbCl5;  molybdenum  pentachloride,  MoCl5;  iodine,  sulphur,  phos- 
phorus or  metallic  iron,  the  last  four  forming  first  their  respective 
halide  compounds.  The  organic  compound  pyridine  (p.  858),  may  also 
be  used.  In  this  way  chlorine  or  bromine  may  be  introduced  into 
the  benzene  ring  atom  by  atom  until  all  six  hydrogens  are  substituted 
as  follows: 

C6H6C1  Mono-chlor  benzene 

C6H4C12  Di-chlor  benzene 

C6H3C13  Tri-chlor  benzene 

C6H2C14  Tetra-chlor  benzene 

C  6HC1 5  Penta-chlor  benzene 

C6C16  Hexa-chlor  benzene 

These  compounds  are  exactly  analogous  to  the  four  chlor  methanes. 
CH3C1  CH2C12  CHC13  CC14 

Mono-chlor  Di-chlor  Tri-chlor  Tetra-chlor 

methane  methane  methane  methane 

In  the  aliphatic  hydrocarbons,  it  will  be  recalled,  substitution  of  the 
halogens  takes  place  by  direct  action  of  the  halogen  in  the  sunlight,  but 
the  best  method  of  preparation  is  from  the  hydroxyl  products  by  action 
of  halogen  acids,  HC1,  HBr,  HI,  or  of  phosphorus  and  the  free  halogen. 
This  reaction  takes  place  in  the  benzene  series  only  with  difficulty.  As 
a  rule  the  substitution  of  halogens  in  the  benzene  ring  by  means  of 
carriers  takes  place  more  easily  than  similar  direct  substitution  of  the 
halogens  (without  carriers)  occurs  in  the  aliphatic  series.  The  two 
series  of  halogen  products  are  also  markedly  different  in  their  reactions, 
and  those  of  the  benzene  series  are  the  more  stable. 

Reactions. — It  will  be  recalled  that  two  important  reactions  of  the 
aliphatic  halides  are  (i)  formation  of  the  hydroxyl  products  by  the 
action  of  silver  hydroxide,  Ag(OH),  (2)  formation  of  amino  products 
by  the  action  of  ammonia. 

CH3(Br  +  Ag)OH    >     CH3— OH  +  AgBr 

Methyl  bromide  Methyl  alcohol 

CH3(Br  +  H)NH2    >     CH3— NH2  +  HBr 

Methyl  bromide  Methyl  amine 

Neither  of  these  reactions  takes  place  with  the  benzene  series  of  halogen 
substitution  products. 


506  ORGANIC  CHEMISTRY 

Fittig's  Reaction. — The  most  important  reaction  of  the  benzene 
halogen  substitution  products  is  what  is  known  as  Fittig's  reaction, 
by  means  of  which  a  paraffin  chain  may  be  substituted  in  the  benzene 
ring,  and  benzene  homologues  prepared. 

C6H5(C1  +  2Na  +  C1)CH3       — >    C6H5— CH3  +  2NaCl 

Mono-chlor  Methyl  Toluene 

benzene  chloride  Methyl  benzene 

This  is  exactly  analogous  to  the  preparation  of  paraffin  homologues 
by  the  Wurtz  reaction. 

CH3(C1  +  2Na  +  C1)CH3       — >     CH3— CH3     +  2NaCl 

Mono-chlor  methane  Ethane 

Benzene  from  Mono-halogen  Benzene. — Nascent  hydrogen  re- 
moves the  halogen  and  reforms  benzene. 

C6H6— Cl  +  2H       — >     C6H6  +  HC1 

Mono-chlor  Benzene 

benzene 

A  very  interesting  fact  is  observed  in  connection  with  the  formation 
of  the  di-halogen  substitution  products.  When  di-brom  benzene  is 
prepared  it  is  almost  entirely  the  para  compound  which  is  formed,  but  at 
the  same  time  a  little  of  the  ortho  but  none  of  the  meta  compound  is 
obtained.  While  it  cannot  be  stated  as  a  definite  law  still  it  may  be 
given  as  a  general  empirical  rule  that  when  the  first  substituting  group 
in  a  benzene  ring  is  Cl,  Br,  7,  OH,  CH3,  or  any  aliphatic  radical,  the 
second  group  entering  the  ring  will  take  either  the  para  or  the  ortho 
position.  Usually  both  compounds  result,  with  a  larger  amount  of  the 
para  product  in  most  cases,  but  no  meta  compound.  On  the  other  hand, 
if  the  first  substituting  group  is  one  of  the  following,  viz.,  CHO,  COOH , 
CN,  NO2,  SOiOH,  then  a  second  group  entering  the  ring  takes  the  meta 
position  only.  Why  this  is  so  is  not  definitely  known  though  stereo 
chemistry  offers  an  explanation. 

With  the  exception  of  the  iodine  substitution  products  of  benzene, 
which  deserve  special  consideration,  the  halogen  products  will  be 
mentioned  only  in  a  tabular  statement  of  their  properties.  They  are 
not  of  any  particular  importance  or  interest. 


HALOGEN  DERIVATIVES 
TABLE  XVIII. — HALOGEN  SUBSTITUTION  PRODUCTS  OF  BENZENE 


507 


M.P. 

B.P. 

Mono-chlor  benzene,  CeHsCl 

Liquid 

-   44  Q°C 

I32°C 

Penta-chlor  benzene,  C6HC16  
Hexa-chlor  benzene,  CCU  

Solid 
colorless 
needles 
Solid 

85.o°C. 
229.  o°C. 

27S°C. 
326°C. 

Mono-brom  benzene,  CeH6Br  

white 
needles 
Liquid 

-  3i-i°C. 

I59°C. 

M 

Di-brom  benzene,  C6H/ 
Br  o  

Liquid 

-     i.o°C. 

224°C. 

m.               

Liquid 

i.o°C. 

220°C. 

Solid 

87  o°C 

2iQ°C 

P. 
Mono-iodo  benzene,  C6H5I  

Di-iodo  benzene,  C6H4/ 

.1          0  

m    

Liquid 

Solid 
Solid 

-   29.8°C. 
i29.40C. 

i88°C. 
285°C. 

2II°C. 

P* 

Solid 

204°C 

Hexa-chlor  benzene  is  formed  by  the  chlorination  not  only  of  ben- 
zene itself,  but  also  of  other  more  complex  hydrocarbons,  e.g.  naphtha- 
lene, anthracene,  phenanthrene,  di-phenyl  methane  (but  notdiphenyl). 
Penta-chlor  benzene  is  of  interest  because  it  was  at  one  time  supposed 
to  exist  in  isomeric  forms  which  is  contrary  to  the  Kekule  theory. 

lodo -benzene. — Five  of  the  iodine  substitution  products  of  benzene 
are  known,  the  hexa-iodo  benzene  having  not  yet  been  prepared.  The 
important  thing,  in  connection  with  the  iodo  benzenes,  is  the  forma- 
tion of  a  group  of  derivatives  not  obtained  from  the  corresponding 
chlorine  or  bromine  products. 

Tri-valent  and  Penta-valent  Iodine. — Iodine,  it  will  be  recalled, 
forms  compounds  in  which  it  acts  either  as  tri-valent  or  penta-valent, 
e.g.  IC18,  IC16,  1,0,,  Ia05. 

Iodo  Benzene  Bichloride  or  Phenyl  lodoso  Chloride. — When  chlo- 
rine gas  is  passed  through  a  chloroform  solution  of  mono-iodo  benzene 
there  is  obtained  a  yellow  crystalline  compound  which  has  the  compo- 
sition of  C6H5— IC12  and  is  known  as  iodo  benzene  di-chloride  or 


508  ORGANIC  CHEMISTRY 

phenyl  iodoso  chloride.    It  easily  decomposes,  by  means  of  potassium 
iodide,  and  goes  back  into  mono-iodo  benzene. 


C6H5— I  +  2C1        >        C6H6— IClj 

Mono-iodo  Phenyl  iodoso 

benzene  chloride 


C6H6— IC12  +  2KT        >        C6H5— I  -h  2KC1  +  I2 

Phenyl  iodoso  Mono-iodo 

chloride  benzene 


Iodoso  Benzene. — If  phenyl  iodoso  chloride  is  treated  with  potas- 
sium hydroxide  or  water  instead  of  with  potassium  iodide,  the  chlorine 
is  replaced  by  oxygen,  and  we  obtain  a  new  compound,  CeHU — IO, 
known  as  iodoso  benzene. 


C6H5— IC12  +  KOH  •*-»        C6H5— IO  +  KC1  +  HC1 

Phenyl  iodoso  Iodoso 

chloride  benzene 


Phenyl  lodonium  Hydroxide. — These  iodoso  compounds  are  de- 
rivatives of  the  hypothetical  base,  C6H5— I(OH)2,  phenyl  iodonium 
hydroxide.  When  a  solution  of  iodoso  benzene  is  heated  it  decomposes 

as  follows: 

• 

2C6H5— 10   >    C6H5— IO2  -h  C6H5— I 

Iodoso  benzene  lodozy  Mono-iodo 

benzene  benzene 

lodoxy  Benzene. — The  reaction  consists  in  a  reciprocal  oxidation 
and  reduction  of  two  molecules  of  the  iodoso  benzene.  One  product  is 
iodo  benzene,  the  other,  viz.,  C6H5 — IO2,  in  which  the  iodine  is  penta- 
valent,  is  known  as  iodoxy  benzene. 

Di-phenyl  lodonium  Hydroxide. — When  iodoso  benzene  and  io- 
doxy benzene,  mixed  in  molecular  proportions,  are  treated  with  silver 
hydroxide  a  strongly  basic  hydroxide  compound  is  obtained  of  the 
formula  (C6H5)2  =  I(OH),  known  as  di-phenyl  iodonium  hydroxide. 

C6H6— 10  +  C6H5— 102  +  AgOH     >      (C6H5)2  =  I(OH)  +  AgIO3 

Iodoso  lodoxy  Di-phenyl 

benzene  benzene  iodonium  hydroxide 


HALOGEN  DERIVATIVES  509 

The  constitution  of  this  compound  may  be  represented  by  the  formula 


:6H5  or  (C6H5)2  =  I(OH) 
^Ott 

Di-phenyl  iodonium  hydroxide 


With  potassium  iodide  it  yields  the  corresponding  iodide  (C6H6)2  =  I  —  I, 
di-phenyl  iodonium  iodide,  which  is  analogous  to  the  quaternary 
tetra-methyl  ammonium  iodide. 


CH 


Tetra-methyl  ammonium  Di-phenyl  iodonium  Iodonium  hydroxide 

iodide  iodide 

Iodonium  Hydroxide.  —  These  iodonium  compounds  are  considered 
as  derivatives  of  a  hypothetical  base,  H2I(OH),  iodonium  hydroxide, 
as  above. 


HALOGEN  SUBSTITUTION  PRODUCTS  OF  BENZENE  HOMOLOGUES 

The  homologues  of  benzene  are  substitution  products  of  benzene 
in  which  an  aliphatic  radical  or  open  chain  group  is  substituted  in  the 
ring.  They  may  be  represented  by  the  general  formula  C6H6-XRX. 

Each  homologous  hydrocarbon,  therefore,  consists  of  two  distinct 
parts,  viz.,  the  benzene  ring  and  the  open  chain  radical;  each  part  pos- 
sessing the  characteristic  properties  belonging  to  it.  By  appropriate 
reactions  substitution  may  be  effected  in  either  one  or  both. 

Substitution  in  Ring,  Substitution  in  Side  Chain. — If  the  substitu- 
tion of  halogens  is  brought  about  through  the  agency  of  carriers  the 
halogen  enters  the  ring,  but  if  it  occurs  in  direct  sunlight  or  at  boiling 
temperature  then  the  halogen  enters  the  side  chain. 

Chlorine  Substitution  Products  of  Toluene. — Taking  toluene,  the 
first  of  the  benzene  homologues,  as  an  illustration  we  have  the  follow- 
ing possible  mono-chlorine  substitution  products,  all  of  which  are 
known. 


ORGANIC  CHEMISTRY 

Substitution  in  Ring,  Chlor  Toluenes.— 

C6H4 

Mi 
/ 


C6H5— CH3-HCl+FeCl2) 


Substitution  in  -Side  Chain. 


Cl 

Mono-chlor  toluenes  (o)  (m)  (p) 


3\ci 

Di-chlor  toluenes  (vie.)  (sym.)  (unsym.) 

CH3 


Cl 

Penta-chlor  toluene 


C6H5— CH2C1 

Benzyl  chloride 
Mono-chlor-methyl  benzene 


^'  C6H5— CHC12 

CtjH5 — CH3+(C1  in  Sunlight) »      Di-chlorSxe^hyTbenzene 

C6H6—  CC1, 

Benzo  tri-chloride 
Tri-chlor-methyl  benzene 

Oxidation  Products  of  Substituted  Toluenes. — The  oxidation  prod- 
ucts of  these  two  groups  of  compounds  are  distinctly  different.     We 


HALOGEN   DERIVATIVES 


have  spoken  of  the  fact  that  when  toluene  itself  is  oxidized  the  methyl 
group  becomes  converted  into  carboxyl,  the  result  being  mono-carboxy 
benzene  or  benzole  acid. 


C6H6—  CH3 

Toluene 


O 


C6H5— COOH 

Benzoic  acid 


Chlor  Toluenes  Yield  Chlor  Benzoic  Acids.— The  five  chlorine  sub- 
stitution products  in  the  first  group  are  made  by  the  action  of  chlorine 
in  presence  of  a  carrier,  the  reaction  for  introducing  halogens  into  the 
benzene  ring.  All  five  of  these  compounds  on  oxidation  yield  a  mon- 
carboxyl  substitution  product  of  benzene,  in  which  there  is  also  sub- 
stituted in  the  benzene  ring  one,  two,  three,  four  or  five  chlorine  atoms. 
This  shows  that  in  these  compounds  the  chlorine  has  entered  the  ring 
leaving  the  side  chain,  methyl,  intact,  which,  by  oxidation,  yields  car- 
boxyl. The  products  are,  therefore,  mono-chlor  to  penta-chlor  benzoic 
acids. 


CeHs — CH3 

Toluene 

C6H4C1— CH3 

Mono-chlor  toluene 

CeH3Cl2 — CH3 

Di-chlor  toluene 

C6H2C13— CH3 

Tri-chlor  toluene 

C6HC14— CH3 

Tetra-chlor  toluene 


O 


O 


O 


+  o 


C6C15—  CH3 

Penta-chlor  toluene 


O 


C6H5— COOH 

Benzoic  acid 

C6H4C1— COOH 

Mono-chlor  benzoic  acid 

C6H3C12— COOH 

Di-chlor  benzoic  acid 

C6H2C13— COOH 

Tri-chlor  benzoic  acid 

C6HC14— COOH 

Tetra-chlor  benzoic  acid 

C6C15— COOH 

Penta-chlor  benzoic  acid 


These  chlorine  substitution  products  of  toluene  are  known  as  chlor- 
toluenes  because  all  of  them  still  have  the  toluene  character,  i.e.  a 
benzene  ring  in  which  one  hydrogen  is  substituted  by  methyl. 

Side  Chain  Substitution  Products  Yield  Benzoic  Acid. — On  oxida- 
tion the  second  group  of  chlorine  products,  made  by  substituting 
chlorine  directly  in  sunlight  without  use  of  a  carrier,  all  yield  the  same 
product,  viz.,  benzoic  acid  or  mono-carboxy  benzene.  This  means  that 
in  them  the  benzene  ring  remains  intact  and  the  side  chain  only  is 
affected  by  the  oxidation.  As  all  of  the  chlorine  is  also  removed  by  the 
oxidation  it  all  must  have  been  in  the  side  chain.  They  are  known, 


512  ORCANIG  CHEMISTRY 

therefore,  as  mono-chlor-methyl,  di-chlor-methyl  and  tri-chlor-methyl 
benzenes,  all  being  mono-substituted  benzenes. 

C6H5— CH3  +  O       >    C6H6— COOH 

Toluene  Benzoic  acid 

Methyl  benzene 

CeHs— CH2C1  +  O    >    C6H5— COOH 

Mono-chlor-methyl 
benzene 

C6H5— CHC12  +  O >    C6H5— COOH 

Di-chlor-methyl 
benzene 

C6H5— CC13  +  O >       C6H5— COOH 

Tri-chlor-methyl 
benzene 

Because,  as  we  shall  see  later,  the  mono-chlor-methyl  benzene 
yields  benzyl  alcohol  it  is  known  as  benzyl  chloride.  The  di-chlor- 
methyl  benzene  similarly  yields  benzaldehyde,  and  is,  therefore,  called 
benzal  chloride,  and  the  third  is  also  called  benzo  tri-chloride. 

We  referred  to  the  fact  that  substitution  in  the  benzene  ring  takes 
place  more  easily  with  toluene  than  with  benzene  itself,  i.e.,  the  presence 
of  a  substituted  methyl  group  increases  the  ease  of  further  substitution 
in  the  ring.  Also  oxidation  takes  place  more  easily  when  substitution 
has  already  occurred  and  still  more  easily  if  the  side  chain  is  likewise 
substituted. 

Isomerism. — As  all  of  the  second  group,  in  which  substitution 
occurs  in  the  side  chain,  considered  as  benzene  derivatives,  are  mono- 
substituted  benzenes,  they  do  not  exist  in  isomeric  forms,  and  only  one 
compound  of  each  formula  is  known.  The  first  group,  however,  in 
which  halogen  substitution  occurs  in  the  ring,  are  all  poly-substitution 
products  of  benzene,  since  toluene  itself  is  a  mono-substituted  benzene. 
Mono-chlor  toluene  is,  therefore,  a  di-substituted  benzene,  and  occurs 
in  the  three  forms,  as  follows : 

ortho-Chlor  toluene  or  i -Methyl  2 -chlor  benzene, 
meta -Chlor  toluene  or  i -Methyl  3 -chlor  benzene, 
para -Chlor  toluene   or  i -Methyl  4-chlor  benzene. 

By  the  ordinary  chlorination  of  toluene  in  presence  of  a  carrier  the  ortho 
(1-2)  and  para  (1-4)  products  are  formed.    Di-chlor  toluene,  in  the 


HALOGEN   DERIVATIVES  513 

same  way  being  a  tri- substituted  benzene,  occurs  in  the  three  forms, 
vicinal,  unsymmetrical  and  symmetrical,  e.g. 

i -Methyl  2-3-di-chlor  benzene, 
i -Methyl  3-4-di-chlor  benzene, 
i -Methyl  3-5-di-chlor  benzene. 

Isomerism  of  the  tri-  and  tetra-  substituted  toluenes  will  not  be  con- 
sidered at  length.  The  chlorine  substitution  products  in  which  more 
than  one  chlorine  is  substituted  may  likewise  occur  in  still  another 
isomeric  form.  Instead  of  the  two  chlorines  or  other  substituting 
elements  or  groups  both  entering  the  ring  or  the  side  chain,  we  may 
have  compounds  in  which  one  or  more  elements  enter  one  position, 
and  at  the  same  time,  one  or  more  enter  the  other  position.  Such  com- 
pounds are  known,  but  will  simply  be  mentioned  by  formula,  e.g. 

C6H4C1— CH2C1 

i-Chlor-methyl  2-chlor  benzene 

C6H3C12— CH2C1 

i -Chlor- methyl   2-3-di-chlor  benzene 

C6H4C1— CHC12 

i-Di-chlor-methyl  2-chlor  benzene 

Halogen  Substitution  Products  of  Higher  Homologues.  —  The 

halogen  substitution  products  of  the  homologues  of  benzene,  above 
toluene,  viz.,  xylene,  mesitylene,  etc.,  need  not  be  discussed  further  than 
simply  to  mention  them.  Of  the  xylenes,  the  para -xylene  is  the  only 
one  yielding  satisfactory  halogen  products.  As  only  one  mono-chlor 
para-xylene  is  possible,  in  which  the  halogen  enters  the  ring,  it  must 
have  the  constitution  i-4-di-methyl  2-chlor  benzene.  In  the  case  of 
mesitylene  also  there  is  only  one  mono-halogen  product,  e.g.  1-3-5- 
tri-methyl  2-iodo  benzene.  Pseudccumene,  which  is  the  1-3-4- 
tri-methyl  benzene,  yields  on  chlorination  by  carriers  a  mixture  of 
three  isomeric  products. 

i-3-4-Tri-methyl  2-chlor  benzene. 
i-3-4-Tri-methyl  5-chlor  benzene. 
i-3-4-Tri-methyl  6-chlor  benzene. 

Halogen  substitution  products  of  the  hydrocarbons  containing 
unsaturated  side  chains  are  also  known,  e.g.  chlor  styrene,  CeHs-CH  = 
CHC1,  phenyl  ethylenyl  chloride  and  iodo  phenyl  acetylene,  C6Hs — 
C  =  CI,  phenyl  acetylenyl  iodide. 

33 


II.  SULPHURIC    AND    SULPHUROUS    ACID    DERIVATIVES 

SULPHONIC  ACIDS 

Sulphuric  Acid  Derivatives. — In  the  aliphatic  series  we  considered 
the  hydroxyl  derivatives  immediately  following  the  halogen  derivatives 
because  in  that  series  the  hydroxyl  compounds  are  directly  and  easily 
prepared  from  the  halogen  substitution  products  by  the  action  of  silver 
hydroxide,  AgOH,  or  sodium  hydroxide,  NaOH.  In  the  benzene  series 
the  halogen  derivatives  are  followed  by  the  sulphuric  acid  derivatives 
because,  in  the  first  place,  the  halogen  derivatives  are  not  converted  into 
hydroxyl  compounds  by  treatment  with  silver  hydroxide,  and  in  the 
second  place,  because  the  sulphuric  acid  derivatives  of  the  benzene 
hydrocarbons  are  easily  formed  directly  from  the  hydrocarbons  by 
action  of  sulphuric  acid,  which  was  not  the  case  in  the  aliphatic  series; 
and  because  they  are  exceedingly  important  as  they  are  readily  trans- 
formed into  other  classes  of  compounds,  e.g.  hydroxyl  compounds, 
phenols. 

Esters. — It  will  be  recalled  that  in  the  aliphatic  series  there  are  two 
classes  of  derivatives  of  sulphuric  acid.  When  sulphuric  acid  reacts 
with  an  alcohol  neutralization  takes  place  between  the  alcohol,  as  a 
base,  and  the  sulphuric  acid;  water,  H — OH,  is  eliminated  and  a  com- 
pound known  as  an  ethereal  salt  or  ester  is  obtained. 

C2H5(OH  +  H)OSO2OH        >        C2H5— OSO2OH 

Ethyl  alcohol  Ethyl  sulphuric  acid 

2C2H6(OH  +  H)OSO2O(H  — >        C2H5— OSO2O— C2HB 

Di-ethyl  sulphate 
Esters 

Sulphonic  Acids. — When,  however,  an  aliphatic  mercaptan  or 
thio-alcohol  is  oxidized  we  obtain  a  compound,  containing  a  sulphuric 
acid  residue,  known  as  a  sulphonic  acid. 

C2H5— SH  +  O  C2H5— SO2OH 

Ethyl  thio-alcohol  Ethyl  sulphonic  acid 


SULPHONIC   ACIDS  515 

The  sulphonic  acids  are  also  formed  in  the  aliphatic  series  by  the 
action  of  a  salt  of  sulphurous  acid  upon  an  alkyl  halide. 

C2H5— I  +  KSO2OH  — >        C2H5— S02OH  +  KI 

Ethyl  iodide  Ethyl  sulphonic  acid 

Though  these  sulphonic  acids  are  isomeric  with  the  esters  of  sul- 
phurous acid  they  do  not  react  like  esters,  i.e.  they  are  not  hydrolyzed 
by  water  or  alkalies  yielding  the  alcohol  and  sulphurous  acid.  We, 
therefore,  represent  the  difference  between  esters  and  sulphonic  acids 
by  the  following  formulas : 

C2H50  C2H60  C2H 

)>SO2  )>SO2 

HCT  c2H5cr  H 

Ethyl  Sulphuric  acid  Di-ethyl  sulphate  Ethyl  sulphonic  acid 

Esters  Sulphonic  acid 

In  the  case  of  the  ester  the  hydrocarbon  radical  replaces  the  hydroxyl 
hydrogen  of  the  sulphuric  acid,  while  in  the  sulphonic  acid  the  radical 
replaces  the  entire  hydroxyl  group  of  the  acid.  In  the  former  the  sul- 
phur of  the  acid  is  linked  to  a  carbon  of  the  radical  through  an  oxygen 
atom,  while  in  the  latter  the  sulphur  is  linked  directly  to  carbon. 

The  sulphonic  acids  of  the  benzene  series  are  exactly  analogous  to 
those  of  the  aliphatic  series,  i.e.  they  are  non-hydrolyzable,  and  are 
represented  by  the  general  formula  R — SO2 — OH.  The  method  of 
preparation  of  the  aliphatic  sulphonic  acids  from  the  halogen  substi- 
tution products  and  a  salt  of  sulphurous  acid  is  not  applicable  in  the 
benzene  series. 

Preparation  of  Benzene  Sulphonic  Acids. — The  method  of  preparing 
benzene  sulphonic  acids  helps  to  explain  and  prove  their  constitution. 
We  have  stated  that  one  of  the  characteristic  distinctions  between  the 
aliphatic  and  benzene  hydrocarbons  is  that  with  the  former  direct  sub- 
stitution of  a  nitric  or  sulphuric  acid  group  does  not  take  place  by  treat- 
ment with  the  acid  itself;  whereas  with  the  latter  such  direct  substi- 
tution takes  place  readily. 

When  benzene  or  a  homologue  is  treated  with  concentrated  or 
fuming  sulphuric  acid  the  hydrocarbon  loses  hydrogen  and  the  acid 


516  ORGANIC  CHEMISTRY 

loses  hydroxyl,  water  being  eliminated,  and  the  sulphonic  acid  of  the 
hydrocarbon  is  formed. 

C6H5(H  +  HO)SO2OH  -»        C6H5—  SO2OH  +  H2O 

(H  +  HO)S02OH  S02OH 


Hc 


L  J 


C  C 

H  H 

Benzene  Benzene  sulphonic  acid 

Therefore,  in  the  sulphonic  acids,  the  sulphuric  acid  residue  (SO2  —  OH) 
is  substituted  in  the  ring,  the  carbon  of  the  ring  being  in  direct  union 
with  the  sulphur  of  the  acid  residue.  The  sulphonic  acids  of  the  ben- 
zene series  are  of  great  importance  while  those  of  the  aliphatic  series 
are  only  slightly  so.  When  benzene  is  treated  with  fuming  sulphuric 
acid,  or  boiled  for  thirty  hours  with  ordinary  concentrated  acid,  benzene 
mono  -sulphonic  acid  is  formed.  By  further  treatment  of  the  mono- 
sulphonic  acid  with  fuming  sulphuric  acid  the  benzene  di-sulphonic 
acid  is  formed  which,  as  stated  on  page  506,  is  the  meta  compound. 

C6H5—  (H  +  HO)—  SO2OH    -  >       C6H5—  S02OH 

Benzene  Benzene  mono-sulphonic  acid 

yS02OH  (i) 
C6H5—  S02OH  +  HO—  SO2OH       —  >     C6H/ 

Benzene  mono-  \c/^  C\1J  f    \ 

sulphonic  acid  bU2U±l  (3) 

Benzene  di-sulphonic  acid  (meta) 

The  para  or  i-4-di-sulphonic  acid  of  benzene  is  also  known  and  likewise 
the  i-3-5-tri-sulphonic  acid. 

Sulphonic  Acids  of  Benzene  Homologues.  —  The  homologues  of 
benzene  react  in  the  same  way  toward  sulphuric  acid  with  the  difference, 
already  mentioned,  that  substitution  takes  place  even  more  easily, 
due  to  the  presence  in  the  ring  of  methyl  or  other  aliphatic  radicals. 
Toluene  sulphonic  acids  are,  therefore,  more  easily  prepared  than 
benzene  sulphonic  acid. 


SULPHONIC   ACIDS 


517 


Toluene  Sulphonic  Acids,  para  and  ortho. — With  the  methyl  group 
already  substituted  in  the  benzene  ring  the  sulphonic  acid  group  enters 
the  para  and  ortho  positions  in  preference  to  the  meta.  If  one  sulphonic 
acid  group  is  substituted  a  second  one  enters  the  position  meta  to  the 
first.  These  facts  are  of  importance  in  connection  with  syntheses  to  be 
considered  later,  e.g.  in  the  preparation  of  saccharin  (p.  712). 

CH3  CH3 


HC 


HC 


O 

c 

H 

Toluene 


CH 


+  HOSO2OH 


CH 


Hc 


L  J 


cH 


and 


S02OH 

para-Toluene 

sulphonic  acid 

i  -Methyl  4-sulphonic 

acid  benzene 

CH3 


:— so2OH 


HC 


HC 


c 

H 

ortho -Toluene 

sulphonic   acid 

i -Methyl    2-sulphonic 

acid  benzene 

The  meta  compound  is  prepared  by  other  methods  (p.  532)  in  which  by 
starting  with  a  toluene  derivative,  in  which  the  ortho  and  para 
positions  are  occupied,  sulphonation  affects  the  meta  position.  The 
ortho  and  para  substituents  are  then  removed.  Sulphonic  acids  of 
xylene,  mesitylene  and  cymene  are  also  known. 

In  the  case  of  the  homologues  of  benzene  we  have  two  different 
types  of  sulphonic  acids  just  as  we  had  of  the  halogen  substitution 
products,  viz.,  (i)  those  in  which  the  sulphonic  acid  group  is  substituted 


518  ORGANIC  CHEMISTRY 

in  the  ring,  and  (2)  those  in  which  it  is  substituted  in  the  aliphatic 
side  chain. 

XCH3 
C6H/  C6H5— CH2SO2OH 

\C/"l  CiTJ  Phenyl  methyl  sulphonic  acid  or 

dU2U±l  Benzyl  sulphonic  acid 

Toluene  sulphonic  acid 
(o.m.p.) 

The  former  are  true  aromatic  sulphonic  acids  prepared  by  direct 
sulphonation,  and  reacting  like  benzene  sulphonic  acid.  The  latter 
are  aliphatic  sulphonic  acids  both  in  methods  of  preparation  and 
reaction. 

Acid  Character. — The  sulphonic  acids  of  the  benzene  hydrocarbons 
are  usually  strongly  acid,  colorless  crystalline  substances,  very  easily 
soluble  in  water.  On  this  account,  in  the  preparation  of  dyes  in  par- 
ticular, the  formation  of  a  sulphonic  acid  is  brought  about  in  order  to 
convert  an  insoluble  hydrocarbon  or  a  derivative  into  an  easily  soluble 
compound.  The  acidity  of  benzene  sulphonic  acid,  CeHs — SO2OH,  like 
the  acidity  of  acid  potassium  sulphate,  KO — SO2OH,  and  ethyl  sul- 
phuric acid,  C2H6O — SO2 — OH,  is  due  to  the  remaining  acid  hydrogen 
of  the  sulphuric  acid.  The  first,  however,  is  an  acid,  the  second  is  an 
acid  salt,  the  third  an  acid  ester.  It  is  extremely  important  in  connec- 
tion with  the  sulphonic  acids,  which  form  such  an  essential  group  of 
compounds  in  the  benzene  series,  to  get  clearly  in  mind  this  difference 
between  sulphonic  acids  and  esters  or  ethereal  salts,  and  the  explanation 
of  the  acid  character  of  the  former.  Benzene  sulphonic  acid  is  mono- 
basic possessing  one-half  the  acidic  properties  of  the  original  sulphuric 
acid.  It,  therefore,  reacts  acid  to  litmus,  and  is  able  to  form  neutral 
salts  with  metals  by  the  replacement  of  the  final  acid  hydrogen  with  a 
metal. 

KO— SO2— O(H  +  HO)— K    >    KO— SO2— OK 

Acid  potassium  Potassium  sulphate 

sulphate  (neutral  salt) 

(acid  salt) 

C6H6— SO2— O(H  +  HO)— K     >     C6H5— SO2— OK 

Benzene  sulphonic  acid  Potassium  benzene  sulphonate 

(an  acid)  (neutral  salt) 

The  general  formula  for  salts  of  the  sulphonic  acids  is,  therefore, 
Ring— SO2— OM. 

Salts  of  Sulphonic  Acids. — The  salts  of  the  sulphonic  acids,  espe- 
cially those  of  sodium,  potassium,  silver,  lead,  barium  and  calcium,  are 


SULPHONIC  ACIDS  519 

usually  crystalline,  but  not  quite  so  easily  soluble  as  the  free  acids. 
Therefore,  to  obtain  pure  sulphonic  acids  it  is  customary  to  convert 
the  acid  first  into  some  one  of  these  salts,  and  then  to  reform  the  free 
acid  by  treatment  of  the  purified  salt  with  sulphuric  acid.  In  the  case 
of  the  barium,  calcium  or  lead  salts  the  metal  is  precipitated  as  an 
insoluble  sulphate. 

C6H5— SO2OH  +  BaCO3    >     (C6H5— SO2O)2Ba  +  H2O  +  CO2 

Benzene  sulphonic  Barium  benzene 

acid  sulphonate 

(C6H6— SO2O)2Ba    +    H2SO4    >     2C6H5— SO2OH    +    BaSO4 

Barium  benzene  sulphonate  Benzene  sulphonic  acid 

The  importance  of  the  sulphonic  acids  of  the  benzene  series  is  due 
to  their  easy  preparation,  and  to  the  variety  of  reactions  which  they 
undergo  in  the  formation  of  other  derivatives. 

Reactions. — The  most  important  reactions  of  the  sulphonic  acids 
are  the  following: 

(i)  Neutralization  forming  salts  as  already  discussed. 

Sulphon  Chlorides. — (2)  Reaction  with  phosphorus  penta-chloride. 
As  sulphonic  acids  contain  the  acid  hydroxyl  group,  they  undergo  the 
characteristic  reaction  with  chlorides  of  phosphorus  and  exchange  the 
hydroxyl  for  chlorine.  The  product  is  known  as  a  sulphon  chloride. 

C6H5— SO2— OH  +  PC15    >    C6H5— SO2— Cl  +  POC13  +  HC1 

Benzene  Benzene 

sulphonic  acid  sulphon  chloride 

This  reaction  is  analogous  to  that  of  acetic  acid  with  phosphorus  penta- 
chloride  by  which  acetyl  chloride  is  formed. 

CH3— CO— OH  +  PC15    >    CH3— CO— Cl  +  POC13  +  HC1 

Acetic  acid  Acetyl  chloride 

Sulphon  Amides. — Just  as  acetyl  chloride  is  converted  into  acet- 
amide  by  the  action  of  ammonia  so  benzene  sulphon  chloride  yields 
benzene  sulphon  amide  by  the  same  treatment. 

C6H5— SO2— (Cl  +   H)NH2        >        C6H5— SO2— NH2 

Benzene  sulphon  Benzene  sulphon  amide 

chloride 

These  two  reactions  by  which  a  sulphonic  acid  is  converted  first 
into  the  sulphon  chloride  and  then  into  the  sulphon  amide  may  be  ap- 
plied with  considerable  ease  to  all  sulphonic  acids.  The  sulphon  chlo- 
ride reacts  further  with  phosphorus  penta-chloride;  all  of  the  sulphur 


520  ORGANIC  CHEMISTRY 

and  oxygen  are  removed,  and  the  halogen  substitution  product  of  the 
hydrocarbon  remains. 

C6H5— SO2— Cl  +   PC15    >    C6H5— Cl   +   SOC12   +   POC13 

Benzene  sulphon  Chlor  benzene 

chloride 

Esters. — (3)  Reaction  with  alcohols.  As  the  sulphonic  acids  are 
acid  compounds  still  containing  one  acid  hydroxyl  they  react  with 
alcohols  forming  esters. 

C6H5— S020(H   +    HO)C2H5        >        C6H5— SO2O— C2H5 

Benzene  sulphonic  acid  Benzene  ethyl  sulphonic  acid  or 

Ethyl  benzene  sulphonate 

This  benzene  ethyl  sulphonic  acid  is  analogous  to  ethyl  sulphuric 
acid,  HOSO2OC2H5,  and  as  the  latter  with  excess  of  alcohol  yields 
ethyl  ether  and  reforms  sulphuric  acid  so  benzene  ethyl  sulphonic 
acid  with  excess  alcohol  yields  ethyl  ether  and  reforms  the  benzene 
sulphonic  acid. 

C6H5— S02O(C2H5  +  C2H5O)H >  C6H5— SO2OH+  C2H5— O— C2H5 

Benzene  ethyl  Benzene  Ethyl  ether 

sulphonic  acid  sulphonic  acid 

These  reactions  of  sulphonic  acids  with  phosphorus  penta-chloride  and 
with  alcohol  both  prove  that  in  sulphonic  acids  there  is  one,  and  only 
one,  acid  hydroxyl  remaining. 

Sulphonic  Acids  to  Hydroxyl  Compounds. — (4)  Reactions  with 
alkalies  by  fusion.  In  the  aliphatic  series  the  most  important  syn- 
thetic reaction  for  the  formation  of  hydroxyl  derivatives  is  the  treat- 
ment of  the  alkyl  halides  with  silver  hydroxide,  which  reaction  we  have 
said  does  not  occur  in  the  benzene  series  when  the  substitution  is  in 
the  ring  and  not  in  the  side  chain.  The  most  important  method  for 
preparing  ring-hydroxyl  compounds  is  by  the  fusion  of  a  sulphonic  acid 
or  its  salt  with  alkalies,  potassium  or  sodium  hydroxide,  a  reaction 
which  does  not  occur  with  the  aliphatic  sulphonic  acids. 

C6H6(SO2OH    +    K)OH        >        C6H5— OH    +    KHSO3 

Benzene  sulphonic  Hydroxy  benzene 

acid  Phenol 

The  other  product  of  the  reaction  is  a  salt  of  sulphurous  acid,  which 
recalls  the  relation  between  the  aliphatic  sulphonic  acids  and  sulphurous 
acid. 

C2H6(C1  +   K)HSO3        >        C2H5— S02OH  +  KC1 

Ethyl  Potassium  Ethyl  sulphonic 

chloride  acid  acid 

sulphite 


SULPHONIC   ACIDS  521 

Cyanides  or  Nitriles. — (5)  Reaction  with  potassium  cyanide.  En- 
tirely analogous  to  the  preceding  reaction  is  that  between  sulphonic 
acids  and  potassium  cyanide.  When  a  sulphonic  acid  is  fused  with 
potassium  cyanide  the  cyanogen  substitution  product  of  the  hydrocarbon 
is  formed 

C6H5(SO2OH  H-  K)CN        >        C6H5— CN  +  KHSO3 

Benzene  sulphonic  Phenyl  cyanide 

acid 

Just  as  the  aliphatic  cyanides  by  hydrolysis  yield  carboxyl  products  or 
acids  so  the  benzene  cyanides  also  yield  acids  on  hydrolysis  and  are, 
therefore,  acid  nitriles. 


H 

C6H5— C(N  +  H 
H 


Phenyl  cyanide 
Benzoic  nitrile 


—OH 


C6H5— COOH  +  NH 


Benzoic  acid 


The  formation  of  cyanogen  products  from  the  sulphonic  acids  is  of 
importance,  therefore,  as  a  step  in  the  formation  of  the  corresponding 
acids. 

Acids  Directly. — (6)  Reaction  with  sodium  formate.  Acids  of  the 
benzene  series  may  also  be  formed  directly  from  the  sulphonic  acids  by 
treatment  with  sodium  formate. 

C6H5(S02OH  +  Na)OOCH    >     C6H5— COOH  +  NaHSO3 

Benzene  sulphonic  Sodium  Benzoic  acid 

acid  formate 

Hydrolysis. — (7)  Reaction  with  water,  hydrolysis.  As  we  have 
stated  in  discussing  the  relation  between  sulphonic  acids  and  sulphuric 
acid  esters  the  former  do  not  hydrolyze  as  do  the  latter,  yielding  the 
acid  and  alcohol.  Hydrolysis  may,  however,  be  brought  about  by  the 
use  of  steam  and  the  products  of  such  reaction  are  the  hydrocarbon  and 
sulphuric  acid. 

C6H5(SO2OH    +    HO)H    >     C6H6    +    HOSO2OH 

Benzene  sulphonic  acid  Benzene 

The  reaction  is  useful  in  preparing  pure  hydrocarbons  as  in  the  case  of 
the  three  isomeric  xylenes.  The  above  reactions  have  been  written  in 
all  cases  with  the  free  acid,  but  in  practice  a  salt,  usually  potassium  or 
sodium,  is  used.  The  reactions  then  are  identical  only  the  potassium 
or  sodium  salt  of  the  other  product  is  formed. 


522  ORGANIC  CHEMISTRY 

Reactions  of  Di-sulphonic  Acids. — The  di-sulphonic  acids  and  tri- 
sulphonic  acids  react  exactly  as  do  the  mono-sulphonic  acids  yielding 
the  corresponding  di  and  /rf-products.  In  the  case  of  the  di-sulphonic 
acids,  however,  which  occur  of  course  as  ortho,  mela  and  para  com- 
pounds, there  are  interesting  rearrangements  which  take  place  so  that  a 
di-sulphonic  acid  does  not  always  yield  a  product  with  the  substituting 
groups  in  the  original  positions.  When  par  a-  di-sulphonic  acid  of  ben- 
zene is  fused  with  potassium  hydroxide  the  di-hydroxyl  product  is 
obtained  (reaction  3),  but  instead  of  being  the  para  compound  it  is 
the  mela.  The  mela  di-sulphonic  acid  of  benzene  by  similar  treatment 
undergoes  no  rearrangement  and  the  mela  compound  is  also  obtained. 

SO2OK  OH 


HC 


with 

.+  2KOH  -4 

k.  ^CH  rearrangement     HC1^      J 


C— OH 


C  C 

H 

SO  OK  meta-Di-hydroxy  benzene 

para-Benzene  di-sulphonic  acid 

SO2OK  OH 


HC  (  CH  no  HC 

U+  2KOH  -4 

C—  SO2OK       rearrangement  HcL  Jc—  OH 

C  C 

H  H 

meta-Benzene  di-sulphonic  acid  meta-Di-hydroxy  benzene 

In  a  similar  way  the  formation  of  di-carboxyl  derivatives  from  the  di- 
cyanogen  products  (reaction  4)  is  subject  to  a  like  rearrangement  in  the 
position  of  the  substituting  groups;  but  the  direct  con-version  of  di- 
sulphonic  acids  into  di-carboxyl  acids  by  treatment  with  sodium  formate 
(reaction  5)  does  not  undergo  any  rearrangement.  As  will  be  under- 


SULPHINIC   ACIDS  523 

stood,  these  facts  are  of  great  importance  in  the  synthesis  of  di-sub- 
stitution  products. 

Summary. — Bringing  together  the  reactions  of  sulphonic  acids  as 
we  have  given  them  we  see  that  either  directly  or  indirectly  they  are 
capable  of  transformation  into  the  following  compounds: 

Sulphonic  acids,  e.g.     C6H5 — SO2 — OH,  may  be  converted  into: 

Salts  (sulphonates)  by  neutralization,  C6H5 — SC>2 — OK 

Sulphon  chlorides,  by  PC15,  C6H5— SO2— Cl 

Sulphon  amides,  from  the  chloride  by  NH3,  C6H5 — SO2 — NH2 

Esters,  by  alcohols,  C6H5— SO2— OC2H5 

Ring  hydroxyl  compounds,  by  alkali  fusion,          CeH5 — OH 
Cyanogen  compounds  (nitriles),  by  KCN  fusion,   C6H5 — CN 
Acids,  by  H— COONa,  or  from  nitriles  by  hydrolysis,  C6H5—  COOH 
Hydrocarbons,  by  steam,  C6H6 

SULPH1N1C  ACIDS 

Sulphurous  Acid  Derivatives. — Just  as  we  have  the  two  acids  of 
sulphur,  sulphuric  and  sulphurous,  differing  from  each  other  by  the 
amount  of  oxygen  present,  so  we  have  benzene  derivatives  of  sul- 
phurous acid  corresponding  to  the  sulphuric  acid  derivatives,  but 
containing  one  atom  of  oxygen  less. 

Sulphinic  Acids. — These  sulphurous  acid  derivatives  are  known 
as  sulphinic  acids  in  distinction  from  sulphonic  acids. 

C6H5— SO3H  or  C6H5— SO2OH        C6H5— SO2H  or  C6H5— SOOH 

Benzene  sulphonic  acid  Benzene  sulphinic  acid 

As  sulphuric  acid  by  reduction  yields  sulphurous  acid  so  the  sul- 
phonic acids  by  reduction  yield  sulphinic  acids.  The  action  takes  place 
better,  however,  if  instead  of  a  sulphonic  acid  we  use  the  corresponding 
sulphon  chloride.  When  benzene  sulphon  chloride  is  treated  with  zinc 
the  zinc  salt  of  the  benzene  sulphinic  acid  is  obtained. 
2C6H5— SO2C1  +  Zn  >  (C6H6S02)2Zn  +  ZnCl2 

Benzene  sulphon  Benzene  sulphinic 

chloride  acid  (Zinc  salt) 

The  free  acid  is  prepared  by  the  action  of  sulphurous  anhydride  upon 
benzene 

C6H6      +      SO2         >         C6H5SO2H 

Benzene  Benzene  sulphinic  acid 

The  sulphinic  acids  are  of  special  interest  because  of  a  phenomenon 
known  as  desmotropism  which  exists  in  these  compounds.  When  the 


524  O   RGANIC  CHEMISTRY 

thio  'ether  or  sulphide  containing  a  benzene  radical  and  an  aliphatic 
radical,  e.g.  C6H5 — S — C2H5,  phenyl  ethyl  thio-ether  or  phenyl  ethyl 
sulphide,  is  oxidized  we  obtain  a  compound  known  as  a  sulphone. 
Sulphones. 

C6H5— S— C2H5    +    O        >        C6H5— S— C2H5 

Phenyl  ethyl  4^ 

thio-ether  "  ^ 

O     O 

Phenyl  ethyl  sulphone 

In  this  compound  both  radicals  are  considered  as  united  directly  to  the 
sulphur.  When  a  salt  of  benzene  sulphuric  acid  is  treated  with  an 
alkyl  halide  a  reaction  resembling  the  Fittig  and  Wurtz  reactions  takes 
place. 

C6H5— SO2(Na    +    I)C2H5         >        C6H5SO2C2H5 

Sodium  benzene  Phenyl  ethyl  sulphone 

sulphinate 

The  product  is  identical  with  that  obtained  from  the  thio-ether,  i.e., 
a  sulphone. 

Formula  for  Sulphuric  Acids. — From  this  it  would  appear  that  the 
formula  for  the  sodium  salt  of  benzene  sulphinic  acid  is  C6H5 — S — Na 


O  O 

and  the  free  acid,  C6H5 — S — H,  and  not  C6H5 — S — OH  as  we  should 


O    O  O 

expect  if  it  is  analogous  to  the  sulphonic  acids  C6H5 — S — OH.     In 


O     O 

such  a  compound  the  acid  hydrogen  is  not  hydroxyl  hydrogen,  but  is 
linked  directly  to  the  sulphur. 

If,  however,  a  sulphinic  acid  salt  is  treated  with  ethyl  chlor  carbonate, 
which  is  C2H5O — C — Cl,  the  elimination  of  NaCl  and  CO2  takes  place 

II 

O 

and  we  obtain  a  compound  of  the  same  composition  as  the  sulphone, 
but  which  is  distinctly  different. 

C6H5— S02(Na+  Cl)— (CO)C2H5 >C6H5— SO2C2H5  +  NaCl  +CO2 

Sodium  benzene 
sulphinate 

(O) 

Ethyl  chlor 
carbonate 


SULPHINIC   ACIDS  525 

Sulphuric  Acid  Ester. — This  compound  is  readily  hydrolyzed  yield- 
ing ethyl  alcohol.  It  must  be,  therefore,  a  true  ester  of  sulphinic 
acid,  and  must  be  represented  by  the  formula 

C6H5— SO— OC2H5 

Ethyl  ester  of  benzene  sulphinic  acid 

Also  this  compound  on  oxidation  yields  a  true  ester  of  sulphonic  acid 
C6H5— SO2— OC2H5 

Ethyl  ester  of  benzene  sulphonic  acid 

In  all  esters  of  oxygen  acids  a  radical  must  be  linked  to  an  oxygen, 
it  having  replaced  a  hydroxyl  hydrogen  in  an  acid,  e.g. 

C6H5— S02— OR  CH3— CO— OR 

Ester  of  benzene  Ester  of  acetic  acid 

sulphonic  acid 

According  then  to  these  reactions  the  formula  of  the  benzene  sul- 
phinic acid  is  exactly  analogous  to  that  of  benzene  sulphonic  acid,  i.e., 

C6H5— SO— OH 

Benzene  sulphinic  acid 

We  have  then  two  constitutions  for  sulphinic  acid  and  its  salts,  each 
one  of  which  is  proven  by  definite  reactions. 

C6H5— S— H  C6H5— S— OH 

x£v  Benzene  Sulphinic  Acid 

s-\       S>L  Desmotropic  Forms  /~\ 

Proven  by  its  relation  .  Proven  by  its  relation 

to  the  sulphones  and  to  sulphonic  acids  and 

the  thio-ethers.  to  true  esters. 

Desmotropism. — Such  a  phenomenon  of  a  single  non-isomeric  com- 
pound giving  definite  evidence  of  existence  in  two  forms  is  known  as 
desmotropism. 

Thio-sulphonic  Acids. — Thio-sulphuric  acid  is  related  to  sulphuric 
in  having  an  oxygen  of  the  latter  replaced  by  sulphur. 

H2SO4  or  HO— SO2— OH  H2S2O3  or  HO— SO2— SH 

Sulphuric  acid  Thio-sulphuric  acid 

In  exactly  the  same  relationship  stand  the  thio-sulphonic  acids  to  the 
sulphonic  acids. 

C6H5— SO2— OH        >        C6H6— SO2— SH 

Benzene  sulphonic  Benzene  thio- 

acid  sulphonic  acid 


526  ORGANIC  CHEMISTRY 

As  thiosulphates  are  made  by  treating  sulphites  with  sulphur  so 
thiosulphonic  acids  result  when  sulphinic  acids  are  treated  with  sulphur. 

H2S03    +    S        -  >        H2S203 

Sulphurous  Thio- 

acid  sulphuric  acid 

C6H5SO2H  -j-  S  —  >        C6H5S02SH 

Benzene  Benzene  thio- 

sulphinic  acid  sulphonic  acid 

Salts  of  thio-sulphonic  acids  are  also  prepared  by  treating  sulphon 
chlorides  with  metallic  sulphides,  e.g.  K2S. 

C6H5SO2C1    +    K2S        -  >        C6H5SO2SK    +    KC1 

Benzene  sulphon  Potassium  benzene 

chloride  thio-sulphonate 

SULPHONES 

Synthesis  of  Sulphones.  —  As  previously  discussed,  these  compounds 
are  direct  oxidation  products  of  the  sulphides  or  thio-ethers. 
C2H5—S—  C2H5  +  O        -  >        C2H5—  S02—  C2H5 

Ethyl  thio-ether  Di-ethyl  sulphone 

Di-ethyl  sulphide 

C6H5—  S—  C6H5  +  O     —  »    C6H5—  SO2—  C6H5 

PhenyJ  thio-ether  Di-phenyl  sulphone 

Di-phenyl  sulphide 

They  may  also  be  made  from  sulphon  chlorides  by  treating  with  a 
hydrocarbon  or  a  halogen  derivative,  in  the  presence  of  A1C13. 
C6H5—  SO2—  Cl  +  C6H6  +  A1C13      -  >      C6H5—  SO2—  C6H5  +  HC1 

Benzene  sulphon  Di-phenyl  sulphone 

chloride 

or    C6H5—  SO2—  Cl  +  C6H5—  Cl  +  A1C18   -  -»    C6H5—  SO2—  C6H4C1 

Phenyl  chlor-phenyl 
sulphone 

By  means  of  this  last  reaction  and  using  in  one  case  benzene  sulphon 
chloride  and  toluene,  and  in  the  second  case  toluene  sulphon  chloride 
and  benzene,  exactly  the  same  phenyl  tolyl  sulphone  is  formed. 

(1)  C6H5—  SO2—  Cl  +  C6H5—  CH3    -  >     C6H5—  SO2—  C6H4—  CH3 

Benzene  sul-  Toluene  Phenyl  tolyl  sulphone 

phon  chloride 

/CH3 

(2)  C6H/  -^ 

Toluene  \o/-\  r*i      i      r*  XT 
sulphon       OU2U1     -f-     <-6*l6 
chloride  Benzene 


x 

C6H/  or    H3C—  C6H4—  SO2—  C6H 

XSO2C«H5 

Tolyl  phenyl  sulphone 


SULPHONES  527 

This  means  that  in  sulphuric  acid  the  two  hydroxyl  groups  are  exactly 
the  same,  for  whichever  one  is  replaced  by  chlorine  and  then  by  a 
hydrocarbon  radical  the  resulting  compound  is  the  same.  Therefore 
sulphuric  acid  must  be 

HO—  S—  OH 


o    o 

Sulphuric  acid 


III.  NITRIC  AND  NITROUS  ACID  DERIVATIVES 
NITRO  COMPOUNDS 

In  the  same  way  in  which  we  have  derivatives  of  the  hydrocarbons 
containing  either  sulphuric  acid  or  sulphurous  acid  groups  so  also  we 
have  derivatives  containing  either  of  the  nitrogen  acid  groups,  i.e. 
nitric  acid,  HNO3,  and  nitrous  acid,  HNO2.  As  in  the  case  of  the 
corresponding  aliphatic  derivatives,  the  two  classes  of  compounds  are 
known  respectively  as  nitro  compounds,  and  nitroso  compounds. 

The  aliphatic  nitro  compounds  are  prepared  by  treating  an  alkyl 
halide  with  silver  nitrite,  AgNO2,  analogous  to  the  preparation  of  the 
sulphonic  acids  by  treating  an  alkyl  halide  with  potassium  acid  sulphite, 
KHSO3.  This  relation,  between  the  organic  derivatives  of  sulphuric 
and  nitric  acids  and  the  salts  of  the  sulphur  and  nitrogen  acids  poorer  in 
oxygen,  is  very  important. 

C2H5— I  +  AgN02        >        C2H5— N02  +  Agl 

Ethyl  Silver  Nitro  ethane 

iodide  nitrite 

C2H5— I  +  KHSO3        >        C2H5— S02— OH  +  KI 

Ethyl  Potassium  Ethyl  sulphonic  acid 

iodide  acid  sulphite 

In  the  benzene  series  the  nitric  acid  derivatives,  like  the  sulphuric 
acid  derivatives,  are  not  prepared  by  this  reaction  with  the  salts  of  the 
oxygen  poorer  acid,  but  are  easily  made  by  direct  treatment  of  the 
hydrocarbon  with  the  acid.  This  direct  sulphonation  and  nitration 
of  the  benzene  hydrocarbons,  remember,  is  one  of  the  characteristic 
differences  between  them  and  their  aliphatic  relatives.  When  benzene 
is  treated  with  concentrated  nitric  acid  or  fuming  nitric  acid,  in  the 
presence  of  sulphuric  acid,  one  or  more  nitric  acid  groups  enter  the 
benzene  ring.  The  reaction  is  exactly  similar  to  the  sulphonation  of  a 
hydrocarbon,  viz.,  hydrogen  from  the  hydrocarbon  and  hydroxyl  from 
the  acid  are  eliminated  as  water,  and  the  acid  group  enters  the  ring  in 
place  of  the  hydrogen. 

528 


NITRO    COMPOUNDS  529 

+  HO—  N02       ->     C6H5—  NO2  +  H2O 

NO2 

(H  +  NO)N02  | 

c  c 


HcL  JcH  HcL  JcH 

C  C 

H  H 

Benzene  Nitro  benzene 

The  sulphonic  acids,  it  will  be  recalled,  are  strong  acids,  their  acid 
character  being  due  to  the  remaining  acid  hydroxyl  left  in  the  com- 
pound. Sulphuric  acid  is  di-basic  and  only  one  of  the  two  hydroxyls  is 
eliminated  by  the  substitution  in  the  ring.  Nitric  acid,  however,  is 
mono-basic  and  possesses  only  one  acid  hydroxyl. 

Not  Acids.  —  When,  therefore,  this  hydroxyl  is  removed  by  the 
reaction  of  nitration  the  residue  contains  no  remaining  acid  hydroxyl 
and  the  compound  can  not  be  acid.  Nitro  benzene  and  the  other 
nitro  compounds  of  this  series  are  unlike  the  sulphonic  acids  then  in 
that  they  are  neutral  compounds. 

Not  Esters,  Non-hydrolyzable.  —  The  nitro  compounds  resemble 
the  sulphonic  acids,  however,  in  that  they  are  non-hydrolyzable,  and, 
therefore,  are  not  esters.  In  them  the  benzene  ring  is  linked  directly 
to  the  nitrogen;  as  in  the  sulphonic  acids  the  ring  is  linked  directly  to  the 
sulphur. 

C6H5—  S—  OH  C6H5—  NO2 

x.>x  Nitro  benzene 

o    o 

Benzene  sulphonic  acid 

Nitro  benzene  can  be  heated  with  water  for  a  long  time  at  200°  without 
decomposition. 

Reduction.  —  Another  reaction  of  the  nitro  compounds  which  proves 
that  the  nitrogen  is  directly  linked  to  the  ring  is  their  reduction  to 
ammonia  derivatives.  As  will  be  explained  more  fully  when  we  take  up 
the  ammonia  derivatives,  just  as  .nitric  acid  by  complete  reduction 
yields  ammonia,  so  nitro  benzene  and  other  nitro  compounds  are 

34 


53°  ORGANIC  CHEMISTRY 

reduced  to  compounds  in  which  an  ammonia  residue  is  substituted 
in  the  ring,  the  nitrogen  being  directly  linked  to  the  carbon.  The 
nitrogen  in  the  nitro  compounds  must  then  also  be  directly  linked  to 
the  carbon  of  the  ring. 

CeHg— NO2     >     C6H5— NH2 

Nitro  benzene  Ammo  benzene 

Di-  and  Tri-nitro  Products.- — By  intensifying  the  action  of  nitra- 
tion (by  heat  or  fuming  nitric  acid)  more  than  one  nitro  group  is  sub- 
stituted in  the  ring,  and  di-  and  /r^'-nitro  derivatives  of  the  hydrocarbons 
result.  In  the  formation  of  the  di-substitution  products  of  benzene  the 
second  nitro  group  enters  the  meta  position. 

Homologous  Nitro  Compounds. — When  the  nitration  of  the  benzene 
homologues  is  effected  by  direct  action  of  the  acid,  as  in  the  case  of 
benzene,  the  nitro  group  enters  the  ring.  In  the  case  of  toluene  it 
takes  the  para  and  ortho  positions.  If  the  nitro  group  is  substituted 
in  the  side  chain  it  is  introduced  by  the  reactions  characteristic  of  the 
aliphatic  nitro  compounds,  i.e.  by  the  action  of  silver  nitrite  upon  a 
halide. 

Nitro  Benzenes 

Mono-nitro  Benzene. — When  benzene  is  treated  with  concentrated 
nitric  and  sulphuric  acids  at  ordinary  temperatures,  or  only  moderate 
heat,  only  one  nitro  group  is  substituted  and  mono-nitro  benzene  is 
the  product.  If  different  proportions  of  the  two  acids  be  used,  or  if 
fuming  nitric  acid  be  added  and  the  mixture  boiled,  then  two  nitro 
groups  are  substituted,  and  di-nitro  benzene  results. 

Mono-nitro  benzene  is  a  pale  yellow  liquid  heavier  than  water;  sp. 
gr.  1.2;  boiling  point  209.4°;  melting  point  +3°.  It  distils  with  water 
vapor  and  is  soluble  in  alcohol.  It  is  known  as  oil  of  mirbane,  but 
because  of  its  resemblance  in  odor  to  oil  of  bitter  almonds  it  is  used  as  a 
substitute  for  the  latter  in  perfumes.  The  chief  importance  of  the 
compound  is  due  to  its  easy  preparation  and  its  transformation  by 
reduction  into  amino  benzene  or  aniline,  through  which  it  becomes  the 
starting  point  in  the  manufacture  of  dyes. 

Di-nitro  Benzene. — Of  the  three  isomeric  di-nitro  benzenes  the 
meta  is  the  one  formed  by  direct  nitration  with  fuming  nitric  acid.  The 
proof  of  its  meta  constitution  is  its  transformation  into  meta  xylene. 


NITRO    COMPOUNDS  531 

It  will  be  recalled  that  the  formation  of  the  di-brom  benzene  resulted 
in  the  para  and  ortho  compounds  and  no  meta;  whereas  the  di-nitro 
benzene  formed  is  the  meta  only.  meta-Di-nitro  benzene  is  a  solid 
crystalline  substance  of  pale  yellow  color,  the  crystals  being  fine  needles ; 
melting  point  90°.  The  ortho  and  para  di-nitro  benzenes  have  been 
prepared  by  other  reactions. 

Tri-nitro  Benzenes. — Of  the  three  isomeric  tri-nitro  benzenes  the 
symmetrical  or  1-3-5  compound  is  the  one  formed  by  intense  direct 
nitration  of  benzene.  The  1-2-4  compound  has  been  made  by  further 
nitration  of  para-di-nitro  benzene. 

Nitro  Toluenes 

The  mono-nit ro  toluenes,  like  the  mono-chlor  toluenes  being  di- 
substituted  benzenes,  are  known  in  the  three  isomeric  forms, 

/CH3 
C«H/ 

NO2(o.m.p.) 

Whereas  when  a  second  nitro  group  enters  a  benzene  ring  in  which  there 
is  one  already  present  it  takes  the  meta  position;  a  nitro  group  entering 
a  ring  in  which  one  methyl  group  is  already  substituted  takes  the  para 
and  ortho  positions  and  not  the  meta.  Therefore,  as  was  previously 
discussed  (p.  506),  the  formation  of  ortho,  meta  or  para  disubstitution 
products  of  benzene  depends  on  the  character  of  the  first  group  sub- 
stituted rather  than  the  second.  In  cases  when  one  isomer  is  not 
formed  by  direct  action  we  can  obtain  it  by  an  indirect  process.  If, 
for  instance,  we  desire  the  meta  compound,  when  by  the  direct  reaction 
the  para  compound  is  formed,  we  proceed  by  first  occupying  the  para 
position  with  a  substituting  group  which  may  afterwards  be  converted 
back  to  hydrogen.  Then  by  direct  substitution  of  the  desired  group, 
entrance  will  be  effected  in  the  position  meta  to  the  first  group.  For 
example,  direct  action  of  nitric  acid  on  toluene  results  in  para -nitro 
toluene.  If  the  following  reactions  are  followed  the  meta-nitro  toluene 
may  be  obtained. 


532 


CH3 


HC 
HC 


LJ 


C 
H 

Toluene 


cn 


ORGANIC  CHEMISTRY 

CH3 

C 

+  HNO3 


NH— OC— CH; 

para-Acetamino 
toluene 


CH3 

C 

CH 

CN02 


CH3 
C 


CNO5 


NH— OC-CH3 

i  -Methyl  3  -nitro 
4-acet  amino  benzene 


Hc 


l.  JcNO, 


C 

I 

NH2 


C 
H 

meta-Nitro  toluene 


By  following  a  similar  plan  any  desired  product  may  be  obtained. 

The  nitro  toluenes  are  of  like  importance  to  nitro  benzene  as  the 
starting  point  in  the  preparation  of  valuable  dyes  of  the  aniline  or 
substituted  ammonia  group. 

Tri-nitro  Toluene.  T.N.T. — One  of  the  nitro  toluenes  is  of  especial 
interest  and  importance  because  of  its  use  as  a  military  high  explosive. 
This  is  tri-nitro  toluene,  commonly  known  as  T.N.T.  Other  names 
also  used  for  the  substance  are,  trotyl,  trinol,  trilite  and  tritolo. 
The  constitution  of  the  compound  is  that  of  the  symmetrical  or  2-4-6- 
tri-nitro  toluene.  As  a  benzene  derivative  it  is,  therefore,  i -methyl 
2-4-6-tri-nitro  benzene. 


NITRO   COMPOUNDS  533 

CH3 
I 

C 
02N— Cr      ^lC— NO2 


'CI 
C 

NO2 

Tri-nitro  toluene 

The  fact  that  strong  nitration  of  toluene  results  in  this  particular  isomer 
is  in  accord  with  the  general  rule  that  a  substituting  group  in  the 
benzene  ring  which  already  has  a  methyl  group  substituted  in  it  takes 
the  para  or  the  ortho  position.  Thus  if  three  nitro  groups  enter  the 
ring  of  toluene  they  should  take  the  two  ortho  and  the  one  para  position 
to  the  methyl,  i.e.  the  2-4-6  positions. 

The  compound  is  made  by  strong  nitration  of  toluene  by  means  of 
nitric  and  sulphuric  acids.  Usually  the  para-  and  ortho-mono-nitro 
toluenes  are  first  prepared  by  a  mild  nitration  with  nitric  acid  alone. 
The  para  compound  being  in  the  excess  is  then  separated  and  used  as 
the  starting  point  for  making  the  tri-nitro  compound.  One  hundred 
parts  of  para-mono-nitro  toluene  are  then  treated  at  6o°-65°  with  a 
mixture  of  75  parts  of  nitric  acid  of  91-92  per  cent  and  150  parts  of 
sulphuric  acid  of  95-96  per  cent.  The  mixed  acid  is  added  slowly  while 
the  warm  toluene  is  stirred.  The  resulting  mixture  is  heated  to  80°  for 
one  half  hour  and  then  allowed  to  cool.  The  crystalline  product,  which 
is  01  tho -para -di-nitro  toluene,  or  i-methyl  i-^-di-nitro* benzene,  m.p. 
69.5°,  is  then  separated  from  the  excess  acid.  The  di-nitro  toluene  is 
dissolved  by  gently  heating  in  four  times  its  weight  of  sulphuric  acid 
of  95-96  per  cent.  Nitric  acid  of  90-92  per  cent  is  then  added  in  an 
amount  equal  to  one  and  one-half  times  the  weight  of  the  di-nitro 
toluene,  the  mixture  being  kept  cool.  Digestion  at  9O°-95°  with 
occasional  stirring  then  follows  for  four  or  five  hours  until  the  evolution 
of  gases  ceases.  The  product  is  then  cooled  and  the  excess  acid 
separated  from  the  crystalline  mass  which  is  washed  with  hot  water  and 
very  dilute  sodium  hydroxide.  On  cooling  to  70°  the  mass  solidifies 
and  is  used  without  further  purification.  The  yield  is  150  parts  of 


534  ORGANIC  CHEMISTRY 

tri-nitro  toluene  from  100  parts  of  di-nitro  toluene.  It  is  somewhat 
poisonous  and  when  recrystallized  from  hot  alcohol  it  forms  white 
crystals  melting  at  81.5°. 

Tri-nitro  toluene  cannot  be  exploded  by  a  flame  nor  by  heating  in 
the  open,  and  is  only  slightly  decomposed  by  striking  it  a  blow.  It  is 
best  exploded  by  means  of  a  detonator  of  fulminate  of  mercury.  It  is 
used  for  military  purposes  in  shells,  bombs  and  submarine  mines.  It 
also  forms  a  constituent  of  many  mixed  explosives.  It  is  about  5 
per  cent  less  powerful  and  also  less  violent  and  less  sensitive  than 
picric  acid  (p.  630),  and  does  not  form  sensitive  salts  or  other  products 
under  storage  conditions  as  does  the  latter.  A  few  examples  may  be 
given  of  mixed  explosives  made  with  tri-nitro  toluene  in  which  ammo- 
nium nitrate  is  used  as  an  oxidizer.  The  presence  of  the  nitrate  weak- 
ens the  power  of  the  T.N.T.,  but  the  mixtures  are  not  very  sensitive 
and  are  adapted  to  military  purposes  and  some  of  them  to  mine  blasting. 

Amatol  is  such  a  mixed  explosive  and  is  used  very  largely  for  shells. 
It  has  varying  proportions  of  the  two  substances;  e.g.,  amatol  40/60 
means  40  per  cent  ammonium  nitrate  and  60  per  cent  T.N.T. 

Ammonal  is  a  mixture  used  for  hand  grenades  and  shells.  Its  com- 
position is  ammonium  nitrate  58.6  per  cent,  aluminium  powder  21.0 
per  cent,  charcoal  2.4  per  cent  and  T.N.T.  18.0  per  cent. 

Faversham  powder  is  a  mixed  explosive  permitted  and  much  used 
in  coal  mines  in  England.  It  is  ammonium  nitrate  47.5  per  cent, 
potassium  nitrate  24  per  cent,  ammonium  chloride  18.5  per  cent  and 
T.N.T.  10  per  cent. 

Nitro  Xylenes 

Of  the  three  isomeric  xylenes,  each  of  which  yields  nitro  products, 
it  is  the  meta-xylene  or  i-3-di-methyl  benzene  which  is  most  easily 
nitrated.  The  number  of  isomeric  nitro  xylenes  possible  has  been  pre- 
viously explained  (pp.  472  and  482).  In  the  case  of  meta-xylene  three 
such  nitro  compounds  are  possible  but  only  one  is  readily  obtained. 
It  is  i-3-di-methyl  4-nitro  benzene ;  that  is,  the  nitro  group  enters  the 
ring  ortho  to  one  methyl  group  and  para  to  the"other.  This  is  just 
what  we  should  expect  from  the  influence  of  the  methyl  group  upon 
subsequent  substitution  (p.  506).  The  nitro  xylenes  are  not  so  impor- 
tant as  nitro  benzene  or  the  nitro  toluenes,  but  have  some  use  in 
dyestuff  manufacture. 


REDUCTION  PRODUCTS    OF   NITRO  BENZENE 


535 


One  of  the  higher  homologues  of  benzene  yields  a  very  interesting 
nitro  product.  When  i -methyl  3 -tertiary  butyl  benzene  is  nitrated 
to  a  tri-nitro  product  the  three  nitro  groups  enter  the  2-4-6  positions. 


O2N— 


NO2 

i -Methyl  3 -tertiary-butyl 
2-4-6-nitro  benzene 

This  compound  is  known  as  artificial  musk  as  it  has  an  odor  very  similar 
to  musk,  and  is  used  as  a  substitute  for  it. 

Nitro -alkyl  Benzenes.— Isomeric  with  nitro  toluene  we  have 
nitro-methyl  benzene,  C6H5 — €H2NO2,  which  belongs  to  the  group  of 
nitro  substitution  products  in  which  nitration  takes  place  in  the  par- 
affin side-chain  and  not  in  the  benzene  ring.  It  must  be  formed,  there- 
fore, not  by  direct  nitration,  but  by  reaction  between  a  halogen-alkyl 
benzene  and  silver  nitrite. 


C6H5— CH2I 

I odo -methyl  benzene 
Benzyl  iodide 


+    AgN02 


C6H5— GH2NO2 

Nitro-methyl  benzene 


REDUCTION  PRODUCTS  OF  NITRO  BENZENE 

The  reactions  of  nitro  substitution  products,  in  which  the  nitro 
group  is  in  the  ring,  are  very  important,  the  nitro  compounds  in  gen- 
eral being  even  more  sensitive  to  reaction  than  the  sulphonic  acids. 
While  the  latter  undergo  several  different  kinds  of  reactions  (p.  519), 
the  nitro  compounds  yield  their  most  important  products  by  one  reac- 
tion only,  viz.,  reduction.  This  one  type  of  reaction,  under  different 
conditions,  yields  a  very  remarkable  series  of  compounds  among  which 
are  included  some  of  the  most  valuable  dye  compounds  known.  Thus 
not  only  in  themselves  are  the  nitro  products  important  but  also  because 
they  are  the  starting  point  for  other  valuable  compounds.  We  may 


536  ORGANIC  CHEMISTRY 

illustrate  these  reduction  products  by  means  of  nitro  benzene,  bearing 
in  mind  that  it  is  typical  of  any  ring  nitro  compound. 

Reduction  of  Nitric  Acid.  —  When  nitric  acid  is  reduced  by  means  of 
hydrogen  we  obtain  as  the  final  reduction  product  ammonia,  NH3. 
That  is,  nitric  acid  and  ammonia  stand  at  the  extremes  of  oxidation  and 
reduction  of  the  element  nitrogen. 


NH,  N  HN03 

Ammonia  Nitrogen  Nitric  acid 

Between  nitric  acid  and  ammonia,  or  between  nitric  acid  and  free 
nitrogen,  stand  the  lower  oxidation  products  of  nitrogen,  viz.,  nitrous 
and  hyponitrous  acids,  or  the  lower  oxides  of  nitrogen,  NO2,  N2O3, 
NO  and  N2O.  In  the  same  way  nitric  acid  substitution  products  are 
reduced  to  ammonia  substitution  products,  i.e.,  nitro  compounds  are  re- 
duced to  amino  compounds. 


C6H5—  NO2  C6H5—  NH2  +  2H20 

Nitro  benzene  Amino  benzene 

Aniline 

In  this  reduction  of  nitro  benzene  to  amino  benzene  or  aniline  several 
intermediate  products  are  formed. 

Alcohol  and  Zinc.  —  When  nitro  benzene  is  reduced  in  a  neutral 
solution,  e.g.,  by  means  of  zinc  dust  in  hot  dilute  alcohol  or  in  hot  water, 
or  by  means  of  aluminium  amalgam  and  water,  the  nitro  benzene  loses 
one  atom  of  oxygen  and  two  atoms  of  hydrogen  are  added.  The  prod- 
uct is  known  as  phenyl  hydroxylamine. 

C6H5-N02  +  2H2  —^          C6H5-NH(OH)  +  H2O 

Nitro  benzene  V^n  T  ^2±l5<Jri;  phenyl  hydroxylamine 

Acid  and  Zinc.  —  When  the  reduction  of  nitro  benzene  takes  place 
in  an  acid  solution,  e.g.,  zinc  and  hydrochloric  acid  or  iron  and  hydro- 
chloric acid,  then  the  reduction  goes  to  the  end  and  the  amino  compound, 
viz.,  aniline,  is  obtained. 

CbH5—  N02  +  3H2     ,_    "rZn     C6H5—  NH2  +  2H20 

Nitro  benzene  (^-n  ~T  -H.L1J  Aniline 

Amino  benzene 

Nitroso-benzene.  —  Intermediate  between  nitro  benzene  and  phenyl 
hydroxyl  amine  is  the  nitrous  acid  derivative  or  nitroso  benzene. 
This  compound  can  not  be  formed  by  reduction  of  the  nitro  benzene, 
but  is  obtained  by  oxidizing  phenyl  hydroxylamine. 

C6H5—  NH(OH)  +  O  -:»        C6H5—  NO  +  H2O 

Phenyl  hydroxyl  Nitroso 

amine  benzene 


REDUCTION   PRODUCTS    OF    NITRO  BENZENE 


537 


Expressing  the  relationship  of  these  three  compounds  in  one  series  of 
reactions  we  have  as  reduction  products  of  nitro  benzene  the  following : 

C6H5— NO2  - 


Nitro 
benzene 


C6H5— NO  ~  —  C6H5— NH(OH) >  C6H5— NH2 

Nitroso  Phenyl  hydroxyl  Aniline 

benzene  amine  Amino  benzene 


Alcoholic  Alkali  and  Zinc. — A  second  series  of  reduction  products  is 
formed  when  the  reduction  takes  place  in  alkaline  solution.  When 
nitro  benzene  is  boiled  with  zinc  in  an  alcoholic  solution  of  an  alkali, 
the  reduction  affects  two  molecules  of  the  nitro  benzene,  which,  by  the 
loss  of  three  atoms  of  oxygen,  become  united  yielding  a  product  known 
as  azoxy  benzene. 

C6H5— N02  +3H2 


CeHs— N02 

Nitro  benzene 


(Zn  +  Ale.  NaOH) 


C6H5— 


C6H5— W 

Azoxy  benzene 


>0  +  3H20 


Aqueous  Alkali  and  Zinc. — When  the  reduction  is  effected  by 
stronger  alkaline  reducing  agents,  e.g.,  zinc  and  aqueous  alkali  or  by 
means  of  sodium  amalgam,  two  molecules  of  nitro  benzene  lose  all  of 
their  oxygen  and  step  by  step  two  and  then  four  atoms  of  hydrogen  are 
added.  The  steps  in  these  reductions  are  as  follows: 

Azo  Benzene,  Hydrazo  Benzene.— 
C6H5— N02          +H          C6H5— N          C6H5— NH          C6H5— NH2 


C6H5— N02  (Zn 

Nitro  benzene 


NaOH)  C6H5— N 

Azo  benzene 


C6H5— NH 

Hydrazo 
benzene 


C6H5— NH2 

Aniline 


We  have  then  the  following  compounds  as  the  reduction  products  of 
nitro  benzene. 

+H  +R2  -O 

c6H5— N02  — >  c6HB— NO  ;m:  c6H5— NHOH  — >  c6H5— NHS 

Mono  nitro         — O  Nitroso  xj       Phenyl  hydroxyl  Amino  benzene 


benzene 


benzene 


TJ 
" 


Aniline 


C6H5— NO,      _  3Q     C6H5— : 


_0       C6H5-N 


C6H5— NO2 

2  Mono-nitro 
Benzene 


C6H5—  N 

Azoxy 
benzene 


C6H6— N 

Azo  benzene 


C6H5— NH 


C6H5— NH2 


C6H5— NH 

Hydrazo 
benzene 


C6H5— NH2 

2  Amino  benzene 
Aniline 


538  ORGANIC  CHEMISTRY 

The  names  azoxy,  azo,  kydrazo  in  the  above  compounds,  and  also 
diazo  which  we  shall  use  presently,  all  come  from  the  French  word  for 
nitrogen,  azote,  and  signify  the  presence  of  nitrogen  in  characteristic 
groupings  which  will  be  more  fully  explained  later  under  each 
compound. 

N1TROSO  COMPOUNDS 

Nitroso  Benzene. — The  nitroso  or  nitrous  acid  derivatives  are  exactly 
analogous  to  the  nitro  or  nitric  acid  derivatives.  As  the  nitro  radical  is 
(NO*),  so  the  nitroso  radical  is  (NO)  and  whenever  this  radical  is 
present,  as  we  found  in  the  nitroso-amines  (p.  61),  and  as  we  shall 
find  in  some  more  complex  compounds  of  the  dye  class,  it  means  nitroso 
derivative.  The  simplest  representative,  viz.,  nitroso  benzene, 
C6H5 — NO,  differs  from  nitro  benzene  in  that  it  is  not  formed  by  the 
direct  action  of  the  acid  on  the  hydrocarbon  nor,  as  shown  above,  is  it 
able  to  be  isolated  as  a  reduction  product  of  nitro  benzene.  It  is 
prepared,  however,  by  the  oxidation  of  phenyl  hydroxyl  amine,  either 
by  means  of  ferric  chloride,  FeCl3,  or  of  chromic  acid,  CrO3. 

C6H5— NH— OH  +  O        >        C6H5— NO 

Phenyl  hydroxyl  Nitroso  benzene 

amine 

The  compound  is  a  crystalline  solid  forming  white  leaflets,  possess- 
ing a  burning  taste.  Its  melting  point  is  68°.  On  melting  it  is  changed 
to  an  emerald  green  liquid  which  is  soluble  in  ether  or  ligroin.  This 
change  in  color  and  state  is  perhaps  caused  by  a  change  from  a  di- 
molecular  arrangement  in  the  white  solid  to  a  mono  -molecular  arrange- 
ment in  the  green  liquid.  Nitroso  benzene  condenses  with  aniline  in 
acetic  acid  solution,  and  is  converted  into  azo  benzene. 

C6H5N 
CsHsNCO    +    H2)NC6H5  ~t  ||    +    H2O 

Nitroso  benzene  Aniline  C  H  N 

Azo  benzene 

Nitroso  derivatives  of  the  other  benzene  hydrocarbons  need  not  be 
considered  individually. 


IV.  AMMONIA  DERIVATIVES  OR  AMINES 
Aniline,  C6H6—  NH2 

Amino  Benzene,  Aniline.  —  The  intermediate  reduction  products 
obtained  from  nitro  benzene  will  be  considered  later  and  we  shall  take 
up  now  the  final  product  of  the  reduction,  viz.,  amino  benzene  or  aniline, 
and  also  important  derivatives  of  it. 

History.  —  Aniline  has  an  interesting  history  and  one  of  especial 
importance  in  connection  with  our  present  ideas  of  the  constitution  of 
organic  compounds.  In  1826,  Unverdorben,  while  working  with 
indigo,  obtained  by  distillation  with  alcohol  a  product  which  formed 
crystalline  salts.  He  called  the  compound  crystalline.  In  1834, 
Zinnin  obtained  a  subtance  from  coal  tar  which  he  called  cyanol.  In 
1840,  Fritzsche,  working  also  on  indigo,  obtained  a  substance  which  he 
called  aniline  from  the  Spanish  word  anil  for  indigo.  In  1842,  Runge 
reduced  nitro  benzene  with  hydrogen  sulphide  and  obtained  a  com- 
pound which  he  called  benzamine.  Finally  in  1843,  Hofmann  worked 
over  these  substances  and  showed  that  they  were  all  the  same  com- 
pound, the  name  aniline  being  retained. 

Substituted  Ammonia.  —  Later  by  a  wonderful  piece  of  work,  which 
we  have  prviously  referred  to  in  discussing  the  constitution  of  the 
amines  (p.  54),  Hofmann  showed  that  this  aniline  and  other  amines 
are  ammonia  compounds  resulting  from  the  substitution  of  organic 
radicals,  either  aliphatic  or  aromatic,  in  place  of  one  or  all  of  the  hydro- 
gen atoms  of  ammonia.  Thus  aniline  and  other  substituted  ammonias 
of  the  benzene  series  are  exactly  analogous  to  the  aliphatic  amines. 

/H  ,CR2  yCeHs 

N^H  N^H  N^H 

H  H  H. 

Ammonia  Methylamine  Aniline 

Phenylamine 

The  salts  of  these  compounds  are: 

H  CH3  C6H6 


H  N     -H  N^  -H 


"C\  C\  Cl 

Ammonium  chloride  Methylamine  Aniline 

hydrochloride  hydrochlonde 

NH4C1  CH3-NH2-HC1  C6HB,-NH2-HC1 

539 


540  ORGANIC  CHEMISTRY 

Preparation  of  Aniline. — In  preparing  aniline,  nitro  benzene  is 
usually  reduced  by  means  of  tin  and  hydrochloric  acid  or  iron  and 
hydrochloric  acid,  the  latter  being  the  commercial  process.  In  the 
reaction  with  tin,  molecular  proportions  of  the  tin  and  acid  must  be 
used  and  the  hydrogen  produced  must  be  sufficient  for  the  reduction  of 
the  nitro  benzene.  The  reaction  proceeds  as  follows: 

C6H£— NO2  +  3Sn  +  6HC1      >      C6H5— NH2  +  2H2O  +  3SnCl2 

Nitro  benzene  Aniline 

A  secondary  reaction  then  takes  place  due  to  the  fact  that  stannous 
chloride  also  reduces  nitro  benzene. 

C6H5— NO2  +  3SnCl2.  +  6HC1       — >    C6H—  NH2  +  2H2O  +  3SnCl4 

As  the  aniline  forms  a  salt  with  hydrochloric  acid  an  extra  molecule  of 
acid  is  required  in  each  of  the  above  reactions.  Taking  account  of 
this  fact  and  combining  the  above  reactions  we  may  write: 

2C6H6— NO2+3Sn+i4HCl        -*    2C6H5— NH2HCl+4H2O+3SnCl4 

At  the  end  of  the  reaction  the  aniline  salt  is  decomposed  with  alkali ,  the 
aniline  being  set  free  and  it  is  then  distilled  with  steam.  The  large 
amount  of  stannic  chloride  present  requires  a  very  large  amount  of 
excess  alkali  in  order  to  prevent  precipitation  of  stannic  hydroxide. 
This  makes  the  distillation  of  the  mixture  difficult  to  carry  out  on  an 
industrial  scale. 

When  the  reducing  agent  is  iron  and  hydrochloric  acid  an  interesting 
side  reaction  takes  place.  Molecular  amount  of  acid  is  not  necessary 
in  this  case,  only  a  small  amount  being  required  sufficient  to  start  the 
reaction  and  form  some  ferrous  chloride.  The  initial  reaction  analogous 
to  the  one  with  tin  takes  place  as  follows: 

C6H5— NO2  +  3Fe  +  6HC1      >      C6H5— NH2  +  3FeCl2  +  2H2O 

Nitro  benzene  Aniline  Ferrous 

chloride 

In  the  presence  of  ferrous  chloride,  however,  metallic  iron  reacts  with 
water  forming  ferric  hydroxide  and  liberating  hydrogen  which  reduces 
the  nitro  benzene.  The  second  stage  of  the  reaction  may  then  be 
written  as  follows: 

C6H5— N02  +  2Fe  +  4H2O     ("t£!^l2)     C6H5NH2  +  2Fe(OH)3 
As  this  requires  no  acid,  only  that  involved  in  the  initial  reaction  need 


AMMONIA  DERIVATIVES    OR   AMINES  541 

be  added.  Also  as  the  acid  is  all  used  the  aniline  remains  as  free  aniline 
and  may  be  distilled  with  steam  without  the  addition  of  any  alkali. 
Thus  the  economy  of  acid  and  technical  ease  of  distillation  makes  this 
second  process  the  one  that  is  used  industrially. 

Aniline  is  a  colorless  liquid  when  pure,  but  it  readily  oxidizes  in  the 
air  and  becomes  dark  colored.  It  melts  at  -80°  and  boils  at  182.5°, 
but  distils  with  steam.  It  is  only  slightly  soluble  in  water,  but  is 
soluble  in  alcohol  and  in  ether.  It  is  present  in  coal  tar  in  small 
amounts  and  also  in  bone  oil,  the  product  of  the  distillation  of  bones. 

Aniline  Dyes. — Aniline  and  many  of  its  derivatives,  also  many 
related  amino  derivatives  of  both  benzene  and  naphthalene  hydro- 
carbons, are  of  great  technical  importance  in  the  manufacture  of  dyes. 
As  the  first  synthetic  dye,  mauve,  was  made  from  aniline  the  name  aniline 
dyes  is  often  used  synonymous  with  coal  tar  dyes  for  all  synthetic 
dyestuffs,  though,  as  we  shall  find,  there  are  several  groups,  some  of 
which  are  in  no  sense  related  to  aniline.  The  dyestuffs  and  the  inter- 
mediate products  connected  with  their  preparation  will  be  referred  to 
as  we  come  to  each  compound. 

Reactions  of  Aromatic  Amines. — (i)  With  acids.  The  first  promi- 
nent reaction  of  aromatic  amines  is  the  one  already  given,  viz.,  with 
acids  they  form  salts.  These  salts  are  soluble  crystalline  compounds, 
which,  like  the  ammonium  salts,  are  easily  decomposed  with  strong 
alkalies  yielding  the  'free  base.  The  reactions  with  aniline  are  as 
follows : 


-H       +HC1  >  N5      H      +KOH >  N-H      +KC1+H2O 


Aniline  \  pi  Aniline 

Aniline 
hydrochloride 

(2)  With  nitrous  acid.  The  reaction  of  the  aromatic  primary  amines 
with  nitrous  acid  is  different  from  that  of  the  aliphatic  primary  amines 
with  the  same  reagent,  and  serves  to  distinguish  the  two  groups  of 
compounds.  When  a  primary  alkyl  amine  is  treated  with  nitrous  acid 
the  hydroxyl  compound  of  the  radical  is  formed  and  all  of  the  nitrogen 
of  the  amine  is  given  off  as  free  nitrogen.  The  reaction  is  as  follows : 

CH3— NH2  +  HN02        >        CH3— OH  +  N2  +  H2O 

Methyl  amine  Methyl  alcohol 


54 2  ORGANIC  CHEMISTRY 

We  may  represent  this  very  clearly  in  this  way : 

Methyl   amine        CH3);— N=!(H2 

+  >     CH3— OH  +  N2  +  H2O 

Nitrous   acid  HO)  i— N=i(O  Methyl  alcohol 

In  this  reaction  there  are  no  intermediate  products. 

When,  however,  a  primary  aromatic  amine  is  treated  with  nitrous 
ricid  an  intermediate  product  is  formed  which  belongs  to  a  group  of 
compounds  that  are  both  very  interesting  and  important.  The  reaction 
with  aniline  is: 

CeHs— NH2  +  HNO2        >         C6H5N2OH  +  H2O 

Aniline  Diazo  benzene 

Phenyl  amine 

or 
Aniline    C6H5— N|=  (H2 

— >        C6H5N2OH  +  H2O 
Nitrous  Acid    HO-N  |  =  (O  Diazo  benzene 

Diazo  Benzene. — The  products  which  may  be  isolated  in  the  form 
of  salts,  if  the  reaction  is  carried  out  in  the  cold,  are  known  as  diazo 
compounds,  aniline  yielding  diazo  benzene.  They  are  strong  bases, 
forming  salts  which  are  often  extremely  explosive  when  dry,  and  very 
unstable  toward  reagents,  undergoing  several  very  important  reactions. 
These  will  be  taken  up  later.  If  the  reaction  is  allowed  to  take  place 
at  ordinary  or  slightly  raised  temperatures  this  intermediate  diazo 
compound  is  not  obtained,  but  the  reaction  completes  itself  just  as  in 
the  case  of  the  aliphatic  amines,  splitting  off  all  of  the  nitrogen  and 
forming  the  hydroxyl  compound  of  the  radical. 

Aniline     C6H5)  j-  N  =!  (H2 

+  — >      C6H6— OH  +  N2  +  H20 

Nitrous  acid       HO)  |  -  N  = !  (O  SfiS? 

Phenol 

(3)  With  carbon  disulphide.  Another  reaction  which  distinguishes 
the  aromatic  amines  from  the  aliphatic  amines  is  the  one  with  carbon 
disulphide.  When  methyl  amine  is'  treated  with  carbon  disulphide 
a  product  is  obtained  according  to  the  following  reaction: 

S(NH3)CH3 
2CH3— NH2  +  CS2  r-»        S(\ 

Methyl  amine  "W  TT PTT 

Methyl  ammonium 
methyl  di-thio-carbamate 


AMMONIA   DERIVATIVES    OR  AMINES 


543 


The  product,  methyl  ammonium  methyl  di-thio-carbamate,  is  an 

alkyl  ammonium  salt,  corresponding  to  the  ammonium  salt,  of  methyl 
di-thio-carbamic  acid  as  shown  by  the  following  formulas  : 


OH 


NH2 

Carbamic 
acid 


SH 

S  =  C<( 

XNH2 

Di-thio-carbamic 
acid 


S  = 


SH 


NH—  CH3 

Methyl  di-thio 
carbamic  acid 


S—  NH4 


NH—  CH3 

Ammonium  methyl 
di-thio-carbamate 


S—  NH3CH3 


NH—  CH3 

Methyl  ammonium 

methyl  di-thio- 

carbamate 


This  reaction  does  not  take  place  with  aromatic  amines.  With  aniline, 
for  example,  there  is  obtained  instead  a  compound  known  as  di-phenyl 
thio-urea,  hydrogen  sulphide  being  eliminated.  On  heating  the  di- 
phenyl  thio-urea  with  acids  one  molecule  of  aniline  is  lost  and  phenyl 
iso-thio-cyanate  is  obtained  (p.  421). 


H)NH—  C6H 


H)NH—  C6H5 

Aniline 


NH—  C6H5 


NH 


,wrl 


Di-phenyl  thio  urea 
Thio-carbamlide 

S  =  C  =  N—  C6H5  +  C6H5—  NH2 

Phenyl  iso-thio-cyanate  Aniline 

Di-phenyl  thio-urea  is  a  di-phenyl  derivative  of  thio-urea,  the  sulphur 
analogue  of  urea. 

NH2 
S  =  C<f 

XNH2 

Thio-urea 


O  =  C<( 
X 


NH 


Urea 


Anilides.  —  (4)  With  organic  acids.  A  final  reaction  to  be  mentioned 
with  the  aromatic  amines  is  that  between  aniline  and  carboxyl  acids. 
Just  as  ammonia  forms  amides  with  organic  acids  so  aniline  forms  com- 
pounds known  as  anilides. 

H)NH2         -  >        CH3—  CO—  NH2  +  H2O 


CH3—  CO(OH 

Acetic  acid 


CH3—  CO—  NH2 

Acetamide 


CH3—  CO(OH 

Acetic  acid 


H)NH—  C6H6 

Aniline 


CH 


CO—  NHC6H5 

Acetanilide 


H2O 


544  ORGANIC  CHEMISTRY 

/CH3  /CH3 

Toluidines,  C6H4<^  Xylidines,  C6H3^-CH3 

XNH2  \NH2 

Homologous  Amines.  Toluidines. — The  amino  derivatives  of  the 
homologues  of  benzene  are  formed  by  the  same  kind  of  reactions  as 
those  for  preparing  aniline,  viz.,  the  reduction  of  the  homologous 
mono-nitro  compounds.  The-  amino  toluenes  in  which  the  ammo 
group  is  substituted  in  the  benzene  ring  are  known  as  toluidines,  and 
there  are,  of  course,  three  isomeric  compounds,  ortho,  meta  and  para. 
In  the  ordinary  nitration  of  toluene  the  ortho  and  para  compounds 
are  formed.  By  indirect  methods  (p.  532)  the  meta-nitro  toluene 
may  also  be  prepared.  These  nitro  compounds  by  reduction  yield  the 
corresponding  toluidines. 

These  three  toluidines  have  nearly  the  same  properties,  e.g.,  melting 
point  and  boiling  point,  but  the  aceto  derivatives  or  acet-toluides, 

H3C— C6H4— NH— OC— CH3 

have  very  different  melting  points  and  differ  in  their  solubility.  This 
permits  a  separation  of  these  isomeric  toluidines  when  it  is  desired. 

m.p.  b.p.  m.p. 

ortho-Toluidine,  -io*5°C.  2i8°C.  ortho-Acet-toluide,  no°C. 
meta-Toluidine,  +i6.o°C.  23O°C.  meta-Acet-toluide,  i53°C. 
para-Toluidine,  +5i.O°C.  234°C.  para-Acet-toluide,  63°C. 

Dyes. — The  toluidines  are  of  great  importance  in  the  manufacture 
of  dyes.  In  making  the  dye  fuchsine  a  mixture  of  aniline  and  ortho- 
and  para-toluidine  is  used,  known  as  aniline  red.  It  is  obtained  by 
starting  with  the  distillation  product  of  coal  tar  known  as  50  per  cent 
benzene  (p.  498),  or  the  fraction  of  light  oil  distillate  boiling  at  no°- 
140°.  This  is  nitrated  and  then  reduced.  In  making  the  dye  safranine 
a  mixture  of  aniline  and  ortho-toluidine  is  used,  and  this  mixture, 
therefore,  is  called  aniline  for  safranine. 

Isomeric  with  the  toluidines  are  the  amino  derivatives  with  the 
amino  group  substituted  in  the  side  chain,  benzyl  amine  or  amino- 
methyl  benzene,  C6H5 — CH2 — NH2.  This  reacts  in  all  ways  like  an 
alkyl  amine. 

Xylidines. — The  amino  derivatives  of  xylene  are  known  as  xylidines, 
and  they  also  are  of  value  for  their  use  in  the  preparation  of  dyes.  The 
technical  xylene,  as  used  for  the  preparation  of  dyestuff  xylidines,  is  a 
mixture  of  ortho-,  meta-,  and  para-xylene  and  the  xylidine  obtained  in 


AMMONIA   DERIVATIVES    OR   AMINES  545 

this  way  is  a  mixture  containing  mostly  the  unsymmetrical  meta-xyli- 
dine,  i.e., 

CH3 


HC 

HcL  JC— CIL 


NH2 

i -3 -Di- methyl  4-amino  benzene 

Technical  Xylidine. — The  para-xylene  is  also  present  in  the  tech- 
nical product  which  of  course  yields  only  one  xylidine,  viz.,  i-4-di- 
methyl  2-amino  benzene.  From  the  0r//w-xylene  present  the  vicinal 
or  i  -2-di-methyl  3-amino  benzene  is  obtained.  The  technical  xylidine 
contains  these  three  isomeric  compounds  and  is  used  in  the  prepara- 
tion of  azo-dyes.  Of  the  amino  derivatives  of  the  higher  homologues 
only  one  will  be  mentioned. 

Pseudocumidine. — Pseudocumene  or  i-2-4-tri-methyl  benzene 
(unsymmetrical)  yields  an  amino  derivative,  viz.,  i-2-4-tri-methyl- 
5-amino  benzene.  It  is  obtained  from  technical  xylidine  by  simply 
heating  with  methyl  alcohol. 

DERIVATIVES  OF  AROMATIC  AMINES 
The  derivatives  of  the  aromatic  amines  are  of  four  kinds. 

1.  Alkyl  or  aryl  anilines,  etc.     Derivatives  formed  by  the  introduc- 
tion of  alkyl  or  aryl  radicals  into  the  amino  group. 

2.  Salts  and  anilides,  etc.     Derivatives  formed  by  the  reaction  of 
acids  with  the  amine  as  an  ammonia  compound. 

3.  Substituted  anilines,  etc.     Derivatives  formed  by  substitution 
in  the  benzene  ring. 

4.  Anilino  acids.     Derivatives  formed  by  substitution  of  the  aro- 
matic amine,  as  an  ammonia  compound,  into  the  hydrocarbon  radical 
of  an  organic  acid. 

In  most  cases  only  the  derivatives  of  aniline  will  be  mentioned,  but 
these  may  be  considered  as  typical  of  corresponding  derivatives  of  the 
other  aromatic  amines. 

35 


546  ORGANIC  CHEMISTRY 

i.  ALKYL  AND  ARYL  ANILINES 

As  aniline,  toluidine,  xylidine,  etc.,  are  primary  amines,  if  we  sub- 
stitute alkyl  or  aryl  radicals  for  one  or  both  of  the  remaining  amirio 
hydrogen  atoms  we  shall  obtain  secondary  and  tertiary  amines.  Such 
products  may  be  typified  by  the  following  in  which  the  methyl  and 
phenyl  radicals  are  substituted  for  the  amino  hydrogen  in  aniline. 

Primary  Secondary  Tertiary 


xe5  ,e5 

N^H  N^-CH,  N 

XH  XH  CH3 

Aniline  Mono-methyl  Di-methyl 

aniline  aniline 


H  C6H5 

Di  -phenyl  Tri  -phenyl 

amine  amine 

These  compounds  are  exactly  analogous  to  mono-methyl  amine, 
primary;  di-methyl  amine,  secondary,  and  tri-methyl  amine,  tertiary; 
and  the  reactions  distinguishing  the  three  groups  of  aromatic  compounds 
are  analogous  to  those  given  for  the  aliphatic  amines  (p.  59).  The 
resulting  products,  however,  are  in  some  cases  distinctly  different, 
showing  a  difference  between  the  paraffin  and  benzene  compounds. 

Reactions  with  Nitrous  Acid.  —  With  nitrous  acid  (HO  —  NO) 
primary  amines,  due  to  the  presence  of  two  remaining  ammonia  hydro- 
gen atoms,  react  with  the  oxygen  of  nitrous  acid  which  is  linked  directly 
to  the  nitrogen  alone.  In  the  case  of  the  alkyl  amines  the  reaction 
does  not  stop  here,  but  the  hydroxyl  group  of  the  nitrous  acid  unites 
with  the  alkyl  radical  forming  an  alcohol  and  the  nitrogen  is  set  free. 

Primary  Amines.  —  With  aromatic  amines  the  reaction  may  be 
stopped  at  the  end  of  the  first  step  and,  as  recently  explained  (p.  542), 
a  new  type  of  compound  known  as  a  diazo  compound  is  obtained. 
This  may  be  decomposed  on  raising  the  temperature  and  the  rest 
of  the  reaction  effected.  This  may  be  illustrated  as  follows: 

/(R  HO) 

N^(H  -*        R—  OH  +  H20  +  N2 

X(H  +  0)=N 

Primary 
amine 


AMMONIA  DERIVATIVES    OR   AMINES 


547 


y(CH3 

N<-(H 


HO) 

+  O)  =  N 


Methyl  amine 
Alkyl  amine 


CH3OH 

Methyl 
alcohol 


(H 

Aniline 

Aromatic 
amine 


O)  =  N—  OH  -  >  H2O 


C6H5N2OH 

Diazo  benzene 


C6H5OH  +  N2 


Hydroxy 
benzene 


Secondary  Amines.  —  With  secondary  amines,  due  to  the  presence 
of  only  one  remaining  ammonia  hydrogen  atom,  the  reaction  involves 
only  the  hydroxyl  group  of  the  nitrous  acid  and  the  nitroso  group, 
(-  —  NO),  enters  the  amine  in  place  of  the  remaining  ammonia  hydrogen. 
In  this  case  the  alkyl  amines  and  the  aromatic  amines  react  alike  as 
follows  : 


R 


(H  +  HO)—  NO 


Secondary 
amine 


/CH 


/R 
Ne-R 

XNO 

Nitroso 

amine 

compound 

/CH3 


+H2O 


+H20 


Di-methyl 
amine 

Alkyl  amine 


(H  +  HO)—  NO 


NO 


Di-methyl  nitroso 
amine 

(A  yellow  oil) 


(H  +  HO)—  NO 


Di-phenyl 
amine 

Aromatic 
amine 


NO 

Di-phenyl 
nitroso 
amine 

(Yellow 
crystals) 


Phenyl  Nitroso  Amine.  —  Under  certain  conditions  aniline,  a  primary 
aromatic  amine,  apparently  undergoes  this  same  reaction  and  yields  a 
nitroso  amine.  If  the  potassium  salt  of  diazo  benzene,  which  is  obtained 
from  aniline  by  the  action  of  nitrous  acid  and  which  will  be  explained 
later  (p.  591),  is  heated,  a  change  takes  place  involving  space  relations. 
The  product  is  isomeric  with  the  diazo  compound  and  is  known  as  the 


548  ORGANIC  CHEMISTRY 

potassium  salt  of  iso-diazo  benzene.  On  acidifying  this  potassium 
salt  we  obtain  the  free  base,  iso-diazo  benzene.  This  undergoes 
rearrangement  and  yields  CeHs  —  NH(NO)  which  is  phenyl  nitroso 
amine.  This  compound  is  the  same  as  would  be  obtained  if  aniline 
underwent  the  nitroso  amine  reaction  characteristic  of  secondary 
amines,  as  just  described. 

Tertiary  Amines.  —  With  the  tertiary  amines,  due  to  the  fact  that 
there  is  no  remaining  ammonia  hydrogen  atom,  no  reaction  with  nitrous 
acid  and  the  amino  group  is  possible.  On  this  account  the  alkyl 
tertiary  amines  undergo  no  reaction  with  this  reagent.  The  aromatic 
tertiary  amines,  however,  do  react  with  nitrous  acid.  As  no  ammonia 
hydrogen  is  present  the  nitrous  acid  reacts  with  a  hydrogen  of  the 
benzene  ring,  and  the  nitroso  group  is  introduced  into  the  ring. 


+  HO—  NO  T-»         no  reaction 


Tri  -methyl 
amine 

Alkyl  amine 

C6H4(H  +  HO)—  NO  C6H4—  NO 


3 
XCH3 


CH 


Di  -methyl  aniline  Nitroso  di  -methyl  aniline 

Aromatic  amine 

In  this  reaction  the  nitroso  group  enters  the  ring  in  the  position  para  to 
the  amino  group. 

N—  (CH3)2  N(CH3)2 


L  JcH  HcL  J 


(H  +  HO)—  NO  NO 

Di-methyl  aniline  para  Nitroso  di-methyl  aniline 

These  reactions  with  nitrous  acid  should  be  considered  in  connection 
with  the  discussion  of  the  action  of  nitrous  acid  on  alkyl  amines  as  given 
in  Part  I,  p.  60. 


AMMONIA   DERIVATIVES    OR   AMINES 


549 


All  of  the  aromatic  amines  with  the  exception  of  tri-phenyl  amine, 
whether  primary,  secondary  or  tertiary,  are  basic  and  form  salts  with 
acids.  The  basic  character  of  the  tertiary  aromatic  amines  varies, 
however,  in  degree  according  to  the  additional  radicals  substituted  for 
the  amino  hydrogen.  On  this  account  they  react  differently  toward  the 
alkyl  halides. 

Reaction  with  Acids  and  with  Alkyl  Halides.  —  As  stated  in  Part  I, 
the  tertiary  alkyl  amines  form  salts,  with  methyl  iodide,  analogous  to 
ammonium  salts.  This  has  been  explained  as  due  to  the  strongly  basic 
character  of  the  tertiary  alkyl  amines  resulting  from  the  substitution 
of  three  methyl  groups  for  three  ammonia  hydrogen  atoms.  With  the 
tertiary  aromatic  amines,  however,  the  acid  character  of  the  phenyl 
group  neutralizes  the  basic  character  of  the  nitrogen,  and  in  case  all 
of  the  ammonia  hydrogen  atoms  are  substituted  by  phenyl  groups  the 
resulting  compound  is  not  basic  enough  to  form  salts  with  alkyl  halides 
or  even  with  acids.  If,  however,  the  tertiary  aromatic  amine  contains 
two  methyl  groups  which  are  basic  in  their  influence  the  compound  is 
then  basic  enough  to  form  salts  with  alkyl  halides. 


CH 


CH3I 


CH3 
CH3 
CH3 


CH3 

Tri  -methyl 
amine 


C6H5  +  CH3I 


Tetra-methyl  ammo- 
nium iodide 


No  salt 


Tri-phenyl 
amine 


CH3I 


N 


CH3 

Di-methyl 
aniline 


Phenyl  tri-methyl 
ammonium  iodide 


Reaction  with  Acetyl  Chloride.—  With  acetyl  chloride  the  amines 
which  contain  at  least  one  ammonia  hydrogen  atom,  i.e.,  primary  and 
secondary,  but  not  tertiary,  react  just  as  ammonia  itself  does  with 


550 


ORGANIC  CHEMISTRY 


the  same  reagent.     The  reaction  takes  place  with  both  alkyl  amines 
and  with  aromatic  amines. 


XH  +  C1)OC— CH3) 
Ammonia  Acetyl  chloride 

:H3 


X 


(H  +  C1)OC—  CH3 

Methyl 
a  mine 

Alkyl 
primary 
amine 


\)C 


— CH3 

Acet-amide 


XOC 


—  CH3 

Acet  methyl  amide 


(H  +  C1)OC—  CH3 

Aniline 

Aromatic 
primary 
amine 

/CH3 


Di-methyl 
amine 

Alkyl 

secondary 

amine 


(H  +  C1)OC—  CH3 


OC— 

Acet-anilide 


CH3 


CH 
XOC 


C—  CH3 

Acet  di-methyl  amide 


(H  +  C1)OC—  CH3 

Mono- 
methyl 
aniline 

Aromatic 

secondary 

amine 


Nf  CH3 
XOC— CH3 

Acet  methyl  anilide 


R 

Tertiary 


C1OC—  CH 


No  reaction 


Mono-methyl  Aniline,  CaH5— NH(CH3) 
Di-methyl  Aniline,  CeHs— N(CH3)2 

The  alkyl  anilines  or  alkyl  phenyl  amines  are  represented  by  the 
above  compounds  which  we  have  already  referred  to  in  the  preceding 


AMMONIA   DERIVATIVES    OR   AMINES  551 

general  discussion  of  derivatives  of  aniline.     Both    are  prepared  by 
treating  aniline  with  a  methyl  halide  or  with  methyl  alcohol  and  a 
halogen  acid. 
C6H5—  NH2  +  CH3—  OH  +  HC1  -  >C6H5—  NH(CH3)  +  HC1  +  H2O 

Aniline  Mono-methyl 

aniline 

C6H5—  NH(CH3)  +  CH3—  Cl        --  >        C6H5—  N(CH3)2  +  HC1 

Mono-methyl  Di-methyl  aniline 

aniline 

In  each  of  the  above  reactions  the  product  obtained  is  the  hydrochloride 
salt  of  the  alkyl  aniline. 

Mono-methyl  aniline,  C6H5NH(CH3),  or  methyl  phenyl  amine, 
is  a  colorless  liquid  boiling  at  193°  with  a  specific  gravity  of  0.976.  In 
preparing  it  by  the  preceding  reaction  it  is  always  obtained  mixed  with 
the  di-methyl  compound.  It  may  be  separated  from  the  latter  by  con- 

/CH3 

version  into  the  non-volatile  acyl  derivative,  viz.,  CeH5  —  N<f  ; 

M)C  —  CH3 

acet  methyl  anilide.  As  the  di-methyl  anilide  has  no  remaining  amino 
hydrogen  it  forms  no  acyl  derivative,  and  after  treatment  of  the  mixed 
alkyl  anilines  with  acetyl  chloride  the  di-methyl  aniline  may  be  dis- 
tilled. 

Nitrosamine  and  para  Nitroso  Methyl  Aniline.  —  The  reaction  with 
nitrous  acid  is  characteristic  of  secondary  amines  and  yields  phenyl 
methyl  nitrosamine,  the  nitroso  group  entering  the  amino  radical. 
This,  however,  undergoes  rearrangement  with  the  transference  of  the 
nitroso  group  to  the  ring  yielding  a  nitroso  benzene  compound. 


/3                  3  y 

N/               N/  N( 

X(H  +HO)—  NO      XNO  |  X 

C  C 


L     JcH      HcL     JcH 


C 
H 

Mono-methyl  Methyl  phenyl  nitrosamine 

aniline 


i-Methyl-amino 
4-nitroso  benzene. 

para-Nitroso 
methyl  aniline 


552  ORGANIC  CHEMISTRY 

Di-methyl  aniline,  C6H5 — N(CH3)2,  is  a  liquid  boiling  at  the  same 
point  as  the  mono-methyl  compound  with  which  it  is  obtained  by  the 
ordinary  method  of  preparation  and  from  which  it  may  be  separated 
by  the  method  just  described.  It  forms  well  crystallized  salts,  especially 
the  double  salt  with  platinum  chloride,  viz.,  C6H5— N(CH3)2.HCL- 
PtCl4.  This  compound  crystallizes,  with  two  molecules  of  water,  in 
ruby  colored  prisms,  which,  on  loss  of  water,  become  reddish-yellow 
plates.  The  acid  oxalate  salt,  C6H5— N(CH3)2.(COOH)2,  forms  large 
rectangular  plates  melting  at  139°.  With  nitrous  acid  the  reaction  is 
the  one  characteristic  of  aromatic  tertiary  amines. 

para-Nitroso  Di-methyl  Aniline. — The  (NO)  group  enters  the  ring 
yielding  directly  a  nitroso  benzene  compound. 

N(CH3)2  (CH8) 

I 
C 

HCrx^\CH 

HcCjcH 

C 

(H  +HO)NO 

Di-methyl  aniline 

This  compound  crystallizes  in  beautiful  large  green  leaves,  melting  point 
85°.  By  reduction  it  goes  to  para-amino  di-methyl  aniline,  and  by 
oxidation  to  para  nitro  di-methyl  aniline. 

(CH3)2  (CH8): 

+  H  JL  +  0 


para-Amino  para-Nitroso  para-Nitro 

di-methyl  aniline  di-methyl  aniline  di-methyl  aniline 


AMMONIA   DERIVATIVES    OR   AMINES  553 

By  boiling  with  KOH  it  is  decomposed  into  the  potassium  salt  of 
nitroso  phenol  and  di-methyl  amine  and  the  di-meth)/l  amine  thus  ob- 
tained is  pure. 

(N(CH8)2  OK 


r^   ^( 
+  H)-OK  -  -> 

:L        JCH  HcL         J( 


HCr^          >CH  HCr  >|CI 

+  NH(CH3)< 
HCL          JCH  HCk  JCH        Dla-rnehyl 


c 


NO  NO 

para -Nitroso 
phenol 

With  aniline  it  forms  addition  products  which  separate  in  beautiful 
steel  blue  needles. 

Methyl  Violet. — A  very  important  reaction  of  di-methyl  aniline  is 
its  conversion,  by  means  of  mild  oxidizing  agents,  into  methyl  violet. 
This  compound  is  a  tri-phenyl  methane  dye  and  the  reactions  involved 
in  its  formation  will  be  explained  later  when  we  study  the  dyes  of  this 
series. 

Rearrangement  of  Alkyl  Anilines. — Both  mono-methyl  aniline  and 
di-methyl  aniline  undergo  an  interesting  rearrangement  when  their 
salts  are  heated  in  sealed  tubes  to  250^3 50°.  The  mono-methyl 
aniline  yields  a  mixture  of  ortho-  and  para-toluidines  while  the  di- 
methyl aniline  yields  first  a  mixture  of  ortho-  and  para-mono-methyl 
toluidines  and  then  finally  from  each  of  these  intermediates  there  is 
obtained  unsymmetrical  meta-xylidine  only. 


554 


ORGANIC  CHEMISTRY 


Mono -methyl  aniline 
HN(CH3).HC1 


CH3 


ortho- 
Toluidine 


para- 
Toluidine 


Di-methyl  aniline 

N(CH3)2.HC1 


H  (CH3).HC1 

N 


H(CH3).HC1 

N 


ortho- 

Mono-methyl 
•  toluidine 


CH3 


para- 

Mono-methyl 
toluidine 


Unsymmetrical  meta-xylidine 
i-Amino  2-4-di-methyl  benzene 


Di-phenyl  Amine,  (CBH6)2  =  NH 
Tri-phenyl  Amine,  (C6H6)3  =  N 

Corresponding  to  the  alkyl  anilines  we  have  the  phenyl  anilines  or 
poly-phenyl  amines. 


C6H5 

Tri-phenyl^amine 


Aniline 

Mono-phenyl  amine 


H 

Di-phenyl  amine 


AMMONIA   DERIVATIVES   OR   AMINES  555 

Di-phenyl  amine  was  discovered  by  Hofmann  in  1864.  It  is  basic 
in  character  but  weaker  than  aniline.  It  is  prepared  by  heating  together 
aniline  hydrochloride  and  aniline  to  240°. 

C6H5—  NH2  +  C6H5—  NH2HC1  —  -»  C6H5—  NH—  C6H5  +  NH4C1 

Aniline  Aniline  Di-phenyl  amine 

hydrochloride 

It  may  be  prepared  also  from  phenol,  aniline  and  zinc. 
C6H5—  NH(H  +  HO)C6H5      (1??      C6H5—  NH—  C6H5  +  H2O 

Aniline  Phenol  Di-phenyl  amine 

This  latter  is  an  important  reaction  for  preparing  the  homologues.     R 
represents  phenyl,  tolyl,  xylyl,  etc. 

CaH5—  NH(H  +  HO)—  R  —  >        C6H6—  NH—  R 

Di-phenyl  amine  crystallizes  from  ligroin  in  white  leaflets  with  faint 
odor;  melting  point  54°,  boiling  point  302°.  It  is  soluble  in  alcohol, 
ether  and  benzene  and  slightly  soluble  in  water.  A  solution  of  di- 
phenyl  amine  in  sulphuric  acid^'.e.,  di-phenyl  amine  sulphate,  is  colored 
blue  by  a  trace  of  nitric  acid,  and  is  used  as  a  test  for  nitrates.  In  the 
color  industry  di-phenyl  amine  makes  azo  dyes. 

Tri-phenyl  amine  is  prepared  by  treating  a  boiling  solution  of 
sodium  in  di-phenyl  amine  with  brom  benzene.  The  acid  influence  of 
the  phenyl  radicals  gives  to  di-phenyl  amine  the  property  of  forming  a 
sodium  compound  which  then  reacts  with  the  brom  benzene. 


Na        -  >         (C6HB)2  =  N—  Na 

Di-phenyl  amine  Sodium  di-phenyl  amine 

(C6H5)2  =  N(Na  +  Br)C6H5        -  >         (C6H5)3  =  N  +  NaBr 

Sodium   di-phenyl  Brom  Tri-phenyl 

amine  benzene  amine 

It  crystallizes  from  ether  in  large  pyramidal  crystals;  melting  point 
127°.  It  is  soluble  in  hot  alcohol,  and  a  little  in  cold  alcohol.  It  has 
lost  all  of  the  basic  properties  of  the  ammonia  and  does  not  form  salts 
with  acids.  This  shows  the  negative  or  acid  influence  of  the  phenyl 
radical  as  compared  with  the  methyl  radical. 

2.  SALTS  AND  AN1L1DES,  ETC. 

The  salts  of  aniline  and  its  homologues  are  the  simplest  derivatives 
which  the  aromatic  amines  form  with  acids. 

C6H5—  NH2  +  HC1        -  >        C.H6—  NH,.HC1 

Aniline  Aniline  hydrochloride 


556  ORGANIC  CHEMISTRY 

These  compounds  need  no  further  explanation  as  they  were  fully 
discussed  under  the  reactions  of  aniline.  The  hydrochloride,  acetate, 
sulphate  and  nitrate  are  all  common  substances.  They  are  all  soluble 
crystalline  bodies.  The  reactions  of  the  aromatic  amines  with  nitrous 
acid  have  been  discussed. 

Acetanilide,  C6H6— NH— OC— CH3 

With  organic  acids  aniline  forms  not  only  the  salts  just  discussed  but 
also  derivatives  analogous  to  the  amides.  When  aniline  is  treated 
with  acetic  acid  at  ordinary  temperature  the  simple  salt  is  first  obtained. 

C6H5— NH2  +  HOOCCHs        >        C6H5— NH2.HOOCCH3 

Aniline  Acetic  acid  Aniline  acetate 

When  this  is  boiled  for  some  time  water  is  lost  and  acetanilide  is 
obtained. 

C6H6— NH2— HOOC— CH3      >       C6H5— NH— OC— CH3  +  H2O 

Aniline  acetate  Acetanilide 

This  reaction  is  analogous  to  the  formation  of  acetamide  from  ammo- 
nium acetate  by  the  loss  of  water  (p.  145). 

CH3— COONH4        >        CH3— CO— NH2+H2O 

Ammonium  acetate  Acetamide 

The  anilide  is  better  prepared  by  the  ordinary  method  of  introducing 
the  acetyl  group,  viz.,  by  using  acetyl  chloride  or  acetic  anhydride. 

CtiH5— NH(H+C1)OC— CH3    >    C6H5— NH— OC— CH3+HC1 

Aniline  Acetyl  Acetanilide 

chloride 

This  reaction  is  also  analogous  to  the  one  between  ammonia  and  acetyl 
chloride  by  which  acetamide  is  formed. 

NH2(H  +  Cl)— OC— CH3        >        NH2— OC— CH3 

Ammonia  Acetyl  chloride  Acetamide 

Antifebrin. — Acetanilide  is  a  common  medicinal  substance  much 
used  as  a  fever  reducer  under  the  name  of  antifebrin.  It  is  a  solid, 
crystallizing  in  glistening  plates;  melting  point  112°.  It  is  slightly 
soluble  in  cold  water,  readily  in  hot  water.  Though  not  an  ester  it 
easily  hydrolyzes  reforming  aniline  and  acetic  acid.  Other  known 
anilides  formed  from  aniline  and  formic  acid,  oxalic  acid  and  benzoic 


AMMONIA   DERIVATIVES   OR   AMINES  557 

acid,  etc.,  are  known.     Oxalic  acid  forms  two  derivatives,  one  acid 
and  one  neutral,  analogous  to  oxamic  acid  and  oxamide  (p.  272). 

C6H5—  NH—  OC—  H  Formanilide 

C6H5—  NH—  OC 

Oxanilic  acid 
HOOC 
C6H6—  NH—  OC 

Oxanilide 
C6H5—  NH—  OC 
C6H5—  NH—  OC—  C6H5  Benzanilide 

Di-anilides.  —  Aniline  also  yields  di-anilides  in  which  both  amino 
hydrogen  atoms  are  replaced  by  acid  groups,  e.g.,  di-acetanilide, 
C6H5  —  N=(OC  —  CH3)2.  Anilides  are  also  formed  from  the  alkyl 
anilines  of  the  secondary  group  but  not  of  the  tertiary. 

/ 
C6H5—  NH(CH3)         -  >        C6H5—  N< 

Mono-methyl  aniline  OC  _  CH 

Acet  mono  -methyl  anilide 

Toluidides  have  been  referred  to  (p.  544).     The  xylidides  and  other 
homologues  need  not  be  considered  individually. 


3.  SUBSTITUTED  ANILINES,  ETC. 

The  derivatives  of  aromatic  amines  resulting  from  substitution  in 
the  ring  are  of  two  classes:  (a)  Substitution  of  hydrocarbon  radicals. 
(b)  Substitution  of  non-hydrocarbon  groups,  e.g.,  halogens,  nitro, 
nitroso,  sulphonic  acid,  hydroxyl,  carboxyl  groups,  etc.  The  first  class 
is  of  course  identical  with  the'  homologues  of  aniline  which  we  have 
already  considered.  In  the  second  class  the  compounds  containing  the 
hydroxyl  group  or  the  carboxyl  group  substituted  in  the  ring  will  be 
considered  under  the  hydroxyl  and  carboxyl  derivatives  of  benzene, 
i.e.,  the  phenols  and  acids.  This  leaves  for  present  treatment  those 
compounds  formed  by  substituting  in  the  ring  of  aniline  or  its  homo- 
logues a  halogen,  nitroso,  nitro  or  sulphonic  acid  group. 


Halogen  Anilines,  C6H4< 

\Halogen 


558  ORGANIC  CHEMISTRY 

The  direct  chlorination  or  bromination  of  aniline  takes  place  more 
easily  than  that  of  benzene,  the  result  being  the  symmetrical  tri-chlor 
or  tri-brom  aniline,  viz.,  i-amino  2 -4 -6 -tri-chlor  benzene,  C6H2C13- 
(NH2);  and  i-amino  2 -4 -6 -tri-brom  benzene,  C6H2Br3(NH2).  The 
mono-halogen  anilines  are  prepared  by  reducing  mono-chlor  nitro 
benzenes,  or  by  halogenating  acetanilide  and  then  hydrolyzing. 


/N°2  4-  H  /NH2 

C6H4<^  ±_5         C6H4<^ 

XC1  XC1 

o.-,  m.-,  p.-,  Chlor  o.-,  m.-,  p.-,  Chlor 

nitro  benzene  amino  benzene 

(chlor  aniline) 

NH— OC— CH3 
C6H5— NH— OC— CH3  +  Cl    >     C6H4<  +H2O 

Acetanilide  \Q  > 

Chlor  acetanilide  (p.-,  o.-) 


C6H4<^  +  CH3— COOH 

Chlor  aniline 

(p.-,  o.-) 

^NH2 
Nitroso  Anilines, 

Nitrous  acid  derivatives  in  which  the  nitroso  group  enters  the  ring 
are  formed  by  the  direct  action  of  nitrous  acid  only  in  the  case  of  the 
tertiary  amines,  e.g.,  di-methyl  aniline  as  already  described  (p.  552). 

XN(CH3)2 
C6H5— N(CH3)2  -f-  HO— NO    »    C6H/ 

Di-methyl  aniline  ^NO 

para-Nitroso  di-methyl  aniline 

In  the  case  of  aniline  itself  this  direct  action  with  nitrous  acid  does  not 
occur  as  previously  explained.  By  starting  with  nitroso  phenol, 
however,  the  amino  group  may  be  introduced  in  place  of  the  hydroxyl 
by  direct  action  of  ammonia. 

,OH      -f-      H)NH2  XNH2 

C6H/  -*     C6H/ 

XNO  XNO 

para-Nitroso  phenol  para-Nitroso  aniline 

i-Hydroxy  4-nitroso  i -Amino  4-nitroso  benzene 

benzene 


AMMONIA   DERIVATIVES    OR   AMINES  559 

The  nitroso  substitution  products  of  secondary  amines,  e.g.,  mono- 
methyl  aniline,  C6H5  —  NH(CH3),  are  formed  by  a  rearrangement  of 
the  nitrosamine  which  itself  is  formed  by  the  direct  action  of  nitrous 
acid  on  the  secondary  amine  (p.  547). 


C6H5— N/  >      C6H5— N/ 

X(H  +  HO)NO  XNO 

Mono-methyl  aniline  Phenyl  methyl  nitrosamine 

.CH3 


NO 


k.          J 


H  NO 

Phenyl  methyl  nitrosamine  para  -Nitroso  methyl  aniline 

i-Methyl-amino  4-nitroso  benzene 

/NH2 
Nitro  Anilines,  CeH/ 

XN02 

The  nitration  of  amino  benzene  (aniline)  takes  place  readily,  the 
nitro  group  entering  the  ring  mostly  in  the  ortho  and  meta  positions. 

/NH2 
C6H5—  NH2  +  HO—  NO2       -*    C6H/ 

XNO2 

o.-,  m.-,  p.-,  Nitro  aniline 

Nitration  also  takes  place  directly  with  the  anilides  (acetanilide  or 
benzanilide),  which  may  then  be  hydrolyzed  yielding  nitro  aniline. 
In  this  case  the  para  compound  is  obtained  almost  exclusively. 

,NH—  OC—  CH3 
C6H6—  NH—  OC—  CH3  -f-  HONO2       —  >     C6H/ 

XN02 


H2O 

-»       C6H/         +  CH3—  COOH 
XNO2 


560  ORGANIC  CHEMISRTY 

These  nitro  anilines  known  as  nitranilines,  especially  the  para  and 
meta  compounds,  are  used  in  the  dyestuff  industry  in  making  azo 
dyes. 

Di-methyl  aniline  also  forms  a  known  nitro  product,  but  mono- 
methyl  aniline  does  not.  Di-nitro  products  analogous  to  the  mono- 
nitro  products  are  known  in  some  cases. 

Sulphonic  Acid  Derivatives 


Sulphanilic  Acid,  C6H4 


NH2 


»S02OH 


As  in  the  case  of  halogenation  and  nitration  the  sulphonation  of 
aniline  takes  place  more  easily  than  that  of  benzene  itself.  When 
aniline  is  heated  with  concentrated  or  fuming  sulphuric  acid  the  sul~ 
phonic  acid  group  enters  the  ring  in  the  para  position.  The  first  re- 
action of  the  sulphuric  acid  on  the  aniline  is  of  course  the  formation  of 
the  salt,  aniline  acid  sulphate,  but  this  loses  water  on  heating  and 
yields  the  sulphonic  acid.  . 

-H20 
C6H5— NH2  +  HO— SO2OH  -  -»  C6H5  -  NH2.HO— SO2OH  ~ 

Aniline  Aniline  acid  sulphate 

/NH2 
CeH4v 

XS02OH 

para-Amino  benzene 
sulphonic  acid 
Sulphanilic  acid 

This  compound  is  known  as  Sulphanilic  acid.  It  may  also  be  con- 
sidered as  an  amino  aderivative  of  benzene  sulphonic  acid,  i.e.,  para- 
amino  benzene  sulphonic  acid.  Its  name,  Sulphanilic  acid,  is  in  agree- 
ment with  its  relation  to  aniline  and  sulphuric  acid.  It  is  distinctly 
different  from  sulphonic  acids  of  the  hydrocarbons  in  being  difficultly 
soluble  in  cold  water.  As  we  shall  see  later,  it  is  of  great  importance 
in  the  preparation  of  dyes.  It  is  a  crystalline  compound  soluble  in 
alkalies  as  the  alkali  salt,  but  is  precipitated  as  the  free  acid  on  acidify- 
ing the  solution  of  the  salt. 

Inner  Salt  Constitution. — The  fact  that  the  alkali  salts  of  sulphanilic 
acid  readily  react  with  acetic  anhydride  resulting  in  the  introduction 
of  the  acetyl  radical  into  the  amino  group,  while  the  free  acid  does  not 


AMMONIA   DERIVATIVES    OR   AMINES  561 

so  react,  supports  the  view  that  the  free  acid  is  an  inner  salt  in  which 
there  is  no  free  amino  group. 

NH2  NH2  XNH3— 

CTT  jr  /~i  TT  /  .       f*  "H"  / 

6Al4\  L,6*l4v  ^6*l4\ 

XS02ONa  XSO2OH  XSO2O— 

Sodium  Sulphanilic  acid 

sulphanilate 

The  sulphonic  acids  of  the  aniline  homologues  and  derivatives  are  all 
crystalline  compounds.  Di-sulphonic  acids  of  the  aromatic  amines  are 
also  known. 

4.  ANILINO  ACIDS 

When  ammonia  is  substituted  in  organic  acids  in  place  of  a  hydrogen 
atom  of  the  hydrocarbon  radical  we  obtain  amino  acids. 

CH3— COOH        >        CH2(NH2)— COOH 

Acetic  acid  Amino  acetic  acid 

Aniline  acting  as  ammonia  forms  derivatives  analogous  to  these  called 
anilino  acids. 

Anilino  Acetic  Acid,  CH2(C6HB— NH)— COOH    Phenyl  Glycine 
Analogous  to  amino  acetic  acid  we  have  anilino  acetic  acid,  better 
known  as  phenyl  glycine,  which  is  formed  by  the  action  of  aniline  upon 
chlor  acetic  acid. 
C6H5— NH(H  +  C1)CH2— COOH    >    C6H5— NH— CH2COOH 

Aniline  Chlor  acetic  Anilino  acetic  acid 

acid  Phenyl  glycine 

As  this  is  plainly  a  phenyl  derivative  of  glycine  or  amino  acetic  acid  it 
is  known  as  phenyl  glycine.  Similar  derivatives  of  other  aliphatic 
acids  are  known. 

POLY-AMINO  BENZENES 

One  group  of  ammonia  derivatives  of  the  benzene  hydrocarbons 
has  still  to  be  considered,  viz.,  that  in  which  more  than  one  amino 
group  is  substituted  in  the  hydrocarbon. 

Di-amino  Benzenes,  Phenylene  Di-amines,  C6H4<^ 

When  di-nitro  benzene  is  reduced  we  obtain  di-amino  benzene. 
,NO2  XNH2 

CTT    /  I       TT  f*    TT  / 

6r±4v  Lx6-H.4> 

XN02 

meta-Di-nitro  benzene  meta-Di-amino  benzene 

meta-Phenylene  di-amine 
36 


562  ORGANIC  CHEMISTRY 

As  the  di-nitro  benzene  ordinarily  prepared  is  the  meta  compound  the 
di-amine  obtained  from  it  is  also  meta.  If,  however,  instead  of  reducing 
di-nitro  benzene  we  start  with  the  partially  reduced  product,  viz., 
nitraniline  (p.  559),  which  is  prepared  largely  as  the  para  compound, 
we  then  obtain  the  para-di-amine. 

XNH2  NH 

C6H/          +  H 

^ 


NH2 

para-Nitraniline  para-Di-amino  benzene 

para-Phenylene  di-amine 

The  ortho  di-amino  benzene  prepared  by  the  reduction  of  ortho- 
nitraniline  is  of  special  interest  because  of  certain  condensation  reactions 
which  it  undergoes  with  aldehydes,  ketones  and  nitrous  acid.  The 
meta  compound  also  shows  a  characteristic  reaction  with  nitrous  acid. 
The  para  compound  is  readily  oxidized  and  gives  characteristic  color 
reactions  with  ferric  chloride  and  hydrogen  sulphide.  It  is  of  impor- 
tance in  the  preparation  of  dyes.  All  of  these  di-amines  are  colorless, 
crystalline  solids  which  can  be  distilled. 

They  differ  from  the  mono-amines  in  being  easily  soluble  in  water. 
They  form  salts  with  acids  reacting  with  two  equivalents  because  of  the 
two  amino  groups. 

N(CH3)2 
para  -Amino  Di-methyl  Aniline,  CeH^ 

NH2(p) 

Di-amino  derivatives  of  the  secondary  amines,  mono-methyl  aniline, 
and  the  tertiary  amines,  di-methyl  aniline,  are  also  known.  Of  these 
compounds  the  para-amino  di-methyl  aniline  is  the  most  important 
in  the  dyestuff  industry.  Tri-amino,  tetra-amino,  penta-amino  and 
hexa-amino  derivatives  of  benzene  and  also  penta-amino  toluene  are  all 
known. 

Relation  to  Dyes.  —  The  amino  derivatives  of  benzene  and  its  homo- 
logues,  which  we  have  been  discussing  (pp.  539,  etc.),  form  an  especially 
important  group  of  compounds  in  connection  with  the  manufacture  of 
synthetic  dyes.  Some  of  the  compounds  are  themselves  dyes  while 
others  are  intermediate  products  in  the  preparation  of  dyes.  When  we 
consider  all  of  the  various  forms  in  which  the  amino  group  may  be 
present  and  the  different  relations  which  it  may  have  to  the  benzene 
ring  we  can  not  fail  to  realize  the  vast  possibilities  in  the  preparation  of 
dyes  and  the  industrial  importance  of  these  amino  compounds. 


V.  NITROGEN    COMPOUNDS    INTERMEDIATE    BETWEEN 
NITRO  BENZENE  AND  ANILINE 

Among  the  nitrogen  compounds  of  benzene  we  have  also  those 
intermediate  compounds  formed  in  the  reduction  of  nitro  benzene  to 
aniline  (p.  535).  These  are  as  follows: 

Nitroso  benzene,  C6H5 — NO 

Phenyl  hydroxyl  amine,     C6H5— NH— OH 

C6H5-N 
Azoxy  benzene,  |  yO 

C,Ub—W 

C6H5— N 
Azobenzene, 

C6H5— N 

C6H5— NH 
Hydrazo  benzene, 

C6H5— NH 

Also  related  to  these  and  best  considered  at  this  time  we  have: 
Phenyl  hydrazine,  C6H5— NH— NH2 

Di-azo  benzene,  C6H5 — N2 — OH 

The  first  of  these  compounds,  nitroso  benzene,  has  been  fully  considered 
as  the  nitrous  acid  derivative  of  benzene  (p.  538). 

Phenyl  Hydroxyl  Amine,  C6H5— NH— OH 

When  nitro  benzene  is  reduced  in  neutral  solutions  by  means  of 
zinc  in  hot  water  or  hot  alcohol  or  when  an  ether  solution  of  it  is  reduced 
by  means  of  aluminium  amalgam  and  water,  or  when  it  is  reduced  electro- 
lytically,  the  product  is  phenyl  hydroxyl  amine. 

+  2H2 

C6H5— NO2  C6H5— NH— OH  +  H2O 

Nitro  benzene      (7^     I    TJ  f)\     Phenyl  hydroxyl  amine 

Phenyl  hydroxyl  amine  is  the  phenyl  derivative  of  hydroxyl  amine, 
NH2 — OH,  which  was  considered  in  Part  I  (p.  63).    Like  the  parent 

563 


564  ORGANIC  CHEMISTRY 

substance,  phenyl  hydroxyl  amine  is  a  base  and  forms  salts  with  acids, 
e.g.,  C6H5—  NH—  OH.HC1,  phenyl  hydroxyl  amine  hydrochloride.  It 
is  a  solid  crystallizing  in  silky  needles  which  melt  at  81°.  It  is  slightly 
soluble  in  cold  water  and  quite  easily  in  hot  water,  alcohol,  ether  and  hot 
benzene.  It  is  easily  oxidized  and  reduces  Fehling's  solution. 

Oxidation  Products.  —  With  different  oxidizing  agents  it  yields 
various  products.  Its  water  solution  oxidizes  easily  in  the  air  and 
yields  azoxy  benzene. 

C6H5—  NH—  OH     +  O     C6H5—  N. 

|  \)  +  2H20 
C6H4—  NH—  OH     (air)     C,R,—W 

Phenyl  hydroxyl  amine  Azoxy  benzene 

With  stronger  oxidizing  agents,  e.g.,  chromic  acid,  CrO3,  or  ferric  chlo- 
ride, FeCl3,  it  yields  nitroso  benzene. 

•  C6H5—  NH—  OH        -  >        C6H5—  NO    +    H2O 

Phenyl  hydroxyl  amine  Nitroso  benzene 

When  boiled  with  water  it  is  partly  volatilized,  but  is  mostly  converted 
into  a  mixture  of  nitroso  bnezene,  CeH5  —  NO;  azoxy  benzene, 

C6H6—  Nv  C6H5—  N 

|   /O  and  azo  benzene,  ||  • 

C6H5—  W  C6H5—  N 

It  is  very  sensitive  to  the  action  of  alkalies  and  by  them  is  converted 
first  into  nitro  benzene,  C6H5  —  NO2,  and  then  into  azoxy  benzene. 
Phenyl  Nitroso  Hydroxyl  Amine.  —  Phenyl  hydroxyl*  amine  is  a 
secondary  amine,  one  hydrogen  of  ammonia  being  replaced  by  the 
phenyl  group  and  another  by  the  hydroxyl  group.  With  nitrous  acid, 
therefore,  it  acts  as  secondary  amines  do,  yielding  a  nitroso  amine 


, 

C6H5—  N/  -»C6H5—  N 

\H  +  HO)—  NO 

Phenyl  hydroxyl  amine  Phenyl  nitroso  hydroxyl  amine 

Molecular  Rearrangement  to  para-Amino  Phenol.  —  Phenyl  hydroxyl 
amine  undergoes  an  important  molecular  rearrangement.  When  boiled 
with  mineral  acids  it  is  converted  into  para-amino  phenol. 


INTERMEDIATE   NITROGEN   COMPOUNDS  565 

NH—  OH  NH2 

I  I 

C  C 


HcL  JcH  HcL  JcH 

C  C 

H  OH 

Phenyl  hydroxyl  a  mine  para-Aminophenol 

i-Amino  4-hydroxy  benzene 

The  rearrangement  occurs  also  when  nitro  benzene  is  electrolytically 
reduced  by  immersing  the  cathode  in  nitro  benzene  and  sulphuric  acid 
and  the  anode  in  sulphuric  acid.  Phenyl  hydroxyl  amine  is  first  pro- 
duced and  by  the  above  rearrangement  is  converted  into  para  amino 
phenol.  This  rearrangement  is  analogous  to  the  one  occurring  when 
phenyl  methyl  nitrosamine  goes  over  to  para-nitroso  methyl  aniline 

(P-  559)- 

Benzyl  Hydroxyl  Amine.  —  One  of  the  hydroxyl  amines  of  the  ben- 
zene homologues  is  of  importance  in  illustrating  a  case  of  isomerism. 
The  compound  is  the  hydroxyl  amine  derivative  of  toluene  with  the 
hydroxyl  amine  group  substituted  in  the  side  chain,  i.e.,  it  is  benzyl 
hydroxyl  amine.  The  isomerism  is  due  to  the  different  hydrogen  atoms 
of  the  hydroxyl  amine  which  the  benzyl  group  replaces.  The  two  com- 
pounds are; 

C6Ij5—  CH2—  O—  NH2  C6H5—  CH2—  NH—  OH 

alpha-Benzyl  hydroxyl  beta-Benzyl  hydroxyl 

amine  amine 

In  the  alpha  compound  the  benzyl  group  replaces  the  hydroxyl  hydrogen 
of  hydroxyl  amine  while  in  the  beta  compound  it  replaces  one  of  the 
amino  hydrogens.  There  are  also  known  two  isomeric  di-benzyl 
hydroxyl  amines  and  one  tri-benzyl  hydroxyl  amine. 

C6H5— 
Azoxy  Benzene, 

C6H5— 

Azoxy  benzene  is  the  product  of  the  reduction  of  two  molecules  of 
nitro  benzene  by  means  of  alcoholic  sodium  hydroxide  and  zinc.  The 


566  ORGANIC  CHEMISTRY 

reaction  results  in  the  loss  of  three  atoms  of  oxygen  from  two  molecules 
of  nitro  benzene  and  the  union  of  the  two  molecules  into  one. 

C6H5—  NO2  3H2  C6H5—  N, 

|  )  O  +  3H20 
C6H5—  N02          (Zn  +  Alc.NaOH)          C6H5—  W 

Nitro  benzene  Azoxy  benzene 

As  has  just  been  stated,  it  is  also  formed  by  the  oxidation  of  phenyl 
hydroxyl  amine  even  in  the  air.  In  this  case  there  is  a  loss  of  four 
hydrogens  and  one  oxygen  from  two  molecules. 

C6H5—  NH—  OH  C6H5—  K 

+  0  -»  |  )0  +  2H20 

C6H5—  NH—  OH  CJ5.1—W 

Phenyl  hydroxyl  amine  Azoxy  benzene 

Azoxy  benzene  is  a  crystalline  compound  melting  at  36°,  soluble  in 
alcohol  and  in  ether.  On  reduction  it  passes  to  the  other  intermediate 
products  closer  to  aniline,  viz.,  azo  benzene  andhydrazo  benzene  and 
finally  to  aniline  itself. 

C6H5—  Nv  C6H5—  N 


C6H5—  W  HO—  C6H4—  N 

Azoxy  Benzene  Hydroxy  azo  benzene 

Rearrangement.  —  Like  nitroso  methyl  aniline  and  phenyl  hydroxyl 
amine  it  undergoes  molecular  rearrangement  as  above. 

C6H6—  N 

Azo  Benzene,  •  || 

C6H5—  N 

Nitro  benzene  when  subjected  to  more  energetic  reduction  by  means 
of  aqueous  sodium  hydroxide  and  zinc  loses  all  four  oxygen  atoms  from 
two  molecules  and  the  two  nitrogens  become  linked  together  by  a 
double  bond,  the  product  being  known  as  azo  benzene. 


C6H5—  NO2          +4H2  C6H5—  N 

||  +  4H20 
C6H5—  NO2     (NaOH+Zn)     CCH6—  N 

Nitro  benzene  Azo  benzene 

It  is  also  formed  by  the  further  reduction  of  azoxy  benzene  or  by  the 
oxidation  of  hydrazo  benzene. 


INTERMEDIATE   NITROGEN   COMPOUNDS  567 

From  Nitroso  Benzene  and  Aniline. — The  most  interesting  method 
of  preparing  azo  benzene  is  by  the  condensation  of  nitroso  benzene 
and  aniline. 

-H20 
C6H5— N(0  +  H2)N— C6H5  —         C6H5^N=N— C6H5 

Nitroso  benzene  Aniline  Azo  benzene 

This  reaction  shows  clearly  the  relationship  between  these  three  com- 
pounds. By  reduction  azo  benzene  yields  hydrazo  benzene  and  then 
aniline.  In  this  reduction  the  doubly  linked  nitrogen  group  is  broken 
by  the  addition  first  of  one  hydrogen  atom  to  each  nitrogen  and  then 
by  the  addition  of  one  more  hydrogen  atom  to  each  nitrogen  with  the 
splitting  of  the  double  molecule  into  two  molecules  of  aniline. 

C6H5— N        +H2        C6H5— NH        +H2        C6H5— NH2 
C6H5— N  C6H5— NH  C6H5— NH2 

Azo  benzene  Hydrazo  benzene  Aniline 

Azo  benzene  is  a  solid  forming  glistening  orange-colored  crystals.  It 
melts  at  68°  and  boils  at  295°. 

Homologous  Azo  Compounds. — Azo  toluenes  and  azo  xylenes,  of 
which  there  are  isomeric  forms,  are  known  as  well  as  azo  compounds  of 
other  substituted  benzenes.  Azo  benzene  is  not  usually  prepared  by 
the  reactions  given  above  but  by  other  reactions  to  be  described  under 
derivatives  of  azo  compounds  in  which  group  most  of  the  important  azo 
compounds  will  be  found.  By  these  reactions  azo  compounds  are 
formed  in  which  the  azo  nitrogen  group  links  two  rings  which  .may  be 
alike,  as  in  azo  benzene  or  azo  toluene,  giving  us  symmetrical  com- 
pounds, or  the  two  rings  may  be  unlike,  either  unsubstituted  or  sub- 
stituted, giving  us  unsymmetrical  compounds.  Formulas  for  a  few 
examples  may  be  given. 

Azo  benzene  C6H5— N  =  N — CftH5  Symmetrical 

Azo  toluene  H3C— C6H4— N  =  N— C6H4— CH3  Symmetrical 

Benzene  azo  toluene  C6H5 — N  =  N — C6H4 — CH3          Unsymmelrical 
Amino  azo  benzene     C6H5 — -N  =  N — C6H4 — NH2          Unsymmetrical 
Di-methyl  amino 
azo  benzene  C6H5— N  =  N— C6H4— N(CH3)2  Unsymmetrical 


568  ORGANIC  CHEMISTRY 

Other  azo  compounds  of  the  benzene  homologues  or  other  hydro- 
carbons, or  of  aniline  and  its  derivatives,  need  not  be  considered.  They 
will  either  be  discussed  in  the  next  section  under  derivatives  of  azo 
compounds  or  if  not  discussed  individually  they  will  be  mentioned  in 
connection  with  important  products  made  from  them. 

Azo  Compounds. — The  term  azo  is  derived  from  the  French  word 
for  nitrogen,  viz.,  azote.  Compounds  designated  by  the  name  azo 
or  some  modification  of  it,  e.g.,  azo  benzene,  oxy  azo  benzene,  ammo 
azo  benzene,  hydrazo  benzene,  azoxy  benzene,  etc. ;  represent  a  class 
of  compounds  in  which  two  nitrogen  atoms,  each  of  which  is  linked  to  a 
separate  benzene  ring,  are  directly  linked  to  each  other  by  a  double  or  single 
bond. 

Ring— N  =  N— Ring 

Azo  compound 

In  the  true  azo  compounds,  the  first  three  mentioned  above,  the 
nitrogen  atoms  are  doubly  linked  to  each  other,  while  in  the  hydrazo  and 
azoxy  compounds  the  double  bond  is  broken  by  the  addition  of  a  hydro- 
gen atom  to  each  nitrogen  or  the  second  bond  of  each  nitrogen  is  linked 
to  a  connecting  oxygen  atom  (see  formulas  preceding) .  In  these  com- 
pounds the  benzene  rings  may  be  either  benzene  itself  or  one  of  its 
homologues,  or  they  may  be  one  of  the  more  complex  ring  compounds 
to  be  studied  later.  The  rings  may  have  various  substituting  groups 
in  them  and  these  groups  may  also  contain  nitrogen.  Also  the  two 
rings  may  be  alike  or  different,  yielding  symmetrical  and  unsymmetrical 
azo  compounds.  Whatever  the  modification  may  be,  however,  the 
grouping  above  is  characteristic  of  all  true  azo  compounds. 

Di-azo  Compounds. — Contrasted  with  the  azo  compounds  we  have 
another  group  known  as  the  di-azo  compounds.  As  the  name  indicates 
these  also  contain  two  nitrogen  atoms  and  these  nitrogens  are  also  directly 
linked  to  each  other,  but  only  one  nitrogen  atom  is  linked  to  a  benzene 
ring. 

C6H5— N2— Cl 

Benzene  diazonium  chloride 

The  full  discussion  of  these  diazo  compounds  with  the  explanation  of 
their  constitution  will  come  later;  but,  as  they  are  involved  in  the  prep- 
aration of  some  of  the  azo  compounds,  it  is  necessary  to  introduce  the 
subject  at  this  time.  They  are  formed  by  the  action  of  nitrous  acid 


INTERMEDIATE    NITROGEN    COMPOUNDS  569 

on   the  primary   aromatic  amines.     We  thus  speak  of  diazotizing  an 
amine  or  we  term  the  reaction  diazotization. 


C6H5—  NH2  +  0  =  N—  OH  +  HC1      -  >       C6H5—  N2—  Cl  +  2H2O 

Aniline  Benzene  diazonium 

chloride 
Di-azo  Reaction 


DERIVATIVES  OF  AZO  COMPOUNDS 
AMINO  AZO  COMPOUNDS 

Two  important  classes  of  derivatives'  of  the  azo  compounds  which 
include  some  very  valuable  dyes  are  the  amino  azo  and  hydroxy  azo 
compounds.  The  latter  which  are  also  called  oxy  azo  compounds  are 
derivatives  of  the  azo  compounds  resulting  from  the  substitution  of  one 
or  more  hydroxyl  groups  in  the  rings. 

C6H5—  N  =  N—  C6H4—  OH 

Hydroxy  azo  benzene 

The  amino  azo  compounds  are  exactly  analogous,  having  one  or  more 
amino  groups  in  the  rings. 


C6H5—  N  =  N—  C6H4—  NH2 

Amino  azo  benzene 

Griess  Diazo  Reaction.  —  The  most  important  method  for  preparing 
both  of  these  classes  of  compounds  is  that  of  Griess,  by  means  of  the 
diazo  compounds  (p.  589).  He  found  that  when  a  salt  of  a  diazo  com- 
pound reacts  with  a  hydroxy  benzene  compound  or  with  an  amino 
benzene  compound,  especially  one  containing  a  tertiary  amine  group, 
e.g.,  di-methyl  aniline,  the  following  reactions  take  place  by  which  the 
ring  of  the  diazo  compound  is  coupled,  by  means  of  the  two  nitrogens, 
with  the  ring  of  the  second  compound  thus  forming  an  azo  compound. 

C6H5—  N2—  (Cl  -f  H)C6H4—  OH  -  >C6H5—  N  =  N—  C6H4—  OH 

Benzene  Hydroxy  Hydroxy  azo  benzene 

diazonium  benzene 

chloride  Phenol 

C6H5N2(C1  +  H)C6H4—  N(CH3)2  -  »C6H5—  N  =  N—  C6H4—  N(CH3)2 

Benzene  diazonium  Di-methyl  Di-methyl  amino  azo 

chloride  aniline  benzene 

He  found  that  tertiary  amines  like  di-methyl  aniline  react  easily,  but 
that  primary  amines  react  in  this  way  only  when  there  are  two   such 


57°  ORGANIC  CHEMISTRY 

primary  amine  groups  present  and  in  the  meta  position  to  each  other, 
the  reaction  taking  place  in  weakly  acid  solution. 

Diazo  amino  Compounds. — In  the  case  of  para  primary  di-amines 
and  primary  mono-amines  such  as  aniline,  the  reaction  does  not  take 
place  in  this  way.  It  was  found  later,  however,  that  primary  mono- 
amines  did  yield  azo  compounds  by  a  molecular  rearrangement  of  an 
intermediate  diazo  amino  compound. 

diazo 
C6H5— NH2         -*         C6H5— N2— Cl    +    C6H5— NH2 > 

Aniline  «ia/»fi'r»«  Benzene  Aniline 

reaction  diazonium 

chloride 

rearrangement 
C  6H5— N2— NH— C  6H  5  ~ >  C  6H  5— N  =  N— C  6H4— NH2 

Diazo  amino  benzene  Amino  azo  benzene 

Thus  by  means  of  the  Griess  reaction  it  is  possible  to  start  with  an 
amino  compound,  diazotise  it  and  then  couple  up  the  diazo  compound 
with  an  undiazotized  amino  compound  and  obtain  the  amino  azo 
compound  either  directly  or  after  molecular  rearrangement. 

Aminoazo  Benzene  from  Nitroazo  Benzene. — Another  method  of 
preparing  aminoazo  compounds  is  analogous  to  the  preparation  of  ani- 
line, i.e.,  by  the  reduction  of  the  corresponding  nitro  compound.  When 
azo  benzene  is  nitrated  we  obtain  nitro  azo  benzene  and  this  on  reduc- 
tion yields  amino  azo  benzene. 

C6H5— N=N— C6H5  +  HNO3    >    C6H6— N  =  N— C6H4— NO2 

Azo  benzene  Nitro  azo  benzene 

C6H5— N=N— C6H4— NO2  +  H >C6H5— N  =  N— C6H4— NH2 

Nitro  azo  benzene  Amino  azo  benzene 

Constitution. — Both  of  these  reactions  of  preparation  establish  the 
constitution  of  the  amino  azo  compounds  and  also  of  the  hydroxy 
azo  compounds  as  we  have  represented  them.  While  three  isomers 
are  possible  in  each  case,  depending  on  whether  the  azo  group  and 
the  amino  or  hydroxyl  group  are  in  the  ortho,  meta  or  para  posi- 
tions in  relation  to  each  other,  yet  in  fact  only  ortho  and  para  com- 
pounds are  known  in  most  instances.  The  full  constitution  of  the  ortho 
and  para  amino  azo  benzene  is  then, 


INTERMEDIATE    NITROGEN   COMPOUNDS 


571 


NH2 
C 


CH     Hc 


L  J 


cH 


N=N C 

para-Aminoazo  benzene 


ortho-Aminoazo  benzene 

By  the  Griess  reaction  the  para  compound  is  always  formed  unless, 
in  the  case  of  the  homologues  of  aniline,  e.g.,  in  preparing  the  amino  azo 
toluenes,  the  para  position  is  occupied.  In  this  case  the  ortho  com- 
pound results. 

NH2 


C— N2— (Cl) 

ortho-Diazo  toluene 

(Diazonium  salt) 


H)C 

ortho-Toluidine 


H 
C 


kJ 


-CH3       HC 

-N  =  N 


— CH 


para-Amino  azo 
ortho-toluene 


572 


ORGANIC  CHEMISTRY 


CH< 


HC 
HC 


#£*| 
\>^ 


CH 


CH 


C— N2— (Cl 

para-Diazo  toluene 
(Diazonium  salt) 


— NH2 


para-Toluidine 


H8C—  C 


. 


cH 


-N=N- 


CH 


C—  NH< 


ortho-Amino  azo  para-toluene 


The  ortho  and  para  amino  azo  compounds  differ  in  certain  reactions 
and  the  view  is  held  by  some  that  two  different  formulas  represent  them. 
We  shall  not  take  up  the  discussion  of  this  question  however. 

Amino  azo  compounds  are  in  general  yellow  or  brown  crystalline 
substances  insoluble  or  difficultly  soluble  in  water,  but  soluble  in  alcohol 
or  ether.  They  are  basic  compounds  readily  forming  salts  which  usually 
possess  a  distinctly  different  color  from  that  of  the  free  bases.  As 
amino  compounds  they  are  able  to  be  diazotized  and  converted  into 
still  more  complicated  azo  compounds  in  which  two  azo  groups  are 
present  in  the  molecule  and  which  are  known  as  dis-azo  compounds. 

C6H5— N  =  N— C6H4— N  =  N— C6H5 

Benzene  dis-azo  benzene 

These,  also,  may  yield  amino  and  hydroxyl  derivatives,  e.g.; 
C6H5— N  =  N— C6H4— N  =  N— C6H4— NH2 

Benzene  dis-azo  benzene  aniline 

This,  again,  may  be  diazotized  and  then  coupled  with  a  new  ring  yield- 
ing a  compound  containing  three  azo  groups  and  termed  a  tris-azo 
compound. 


INTERMEDIATE   NITROGEN   COMPOUNDS  573 

The  most  important  derivatives  of  the  amino  azo  compounds  are 
the  sulphonic  acids  of  which  mono-  and  di-sulphonic  acids  are  known. 

Amino  Azo  Benzene,  C6H5— N  =  N— C6H4— NH2 

This  is  the  simplest  amino  azo  compound  and  is  known  in  the  para 
form.  It  is  a  yellow-brown  crystalline  substance  melting  at  126°, 
and  boiling  at  360°.  It  is  soluble  in  alcohol  and  slightly  in  hot  water. 

Aniline  Yellow. — It  is  a  dye  known  as  aniline  yellow  and  is  of  es- 
pecial interest  in  being  the  first  azo  dye  used  (1863),  though  it  was 
first  prepared  by  Griess  in  1859,  by  the  reaction  just  described  (p.  570). 
At  present  it  is  not  used  as  a  dye  to  any  extent.  The  hydrochloride 
salt  is  a  beautiful  violet  colored  substance  which  dissolves  slightly  in 
hot  acids  to  a  red  colored  solution. 

NaO02S— C6H4— N  =  N— C6H4— NH2 

(i)  (4)     (4)  (i) 

and 

(i) 
XNH2 

NaO02S— C6H4— N  =  N— C6H3<( 

XSO2ONa 

(i)  (4)     (4)  (2) 

Acid  yellow 

Acid  Yellow. — A  mixture  of  the  sodium  salts  of  the  mono-  and  di- 
sulphonic  acid  derivatives  of  amino  azo  benzene  is  a  dye  known  as 
acid  yellow  or  fast  yellow,  as  above. 

Di-methyl  Amino  Azo  Benzene,  C6H6— N  =  N— C6H5— N(CH3)2 

Butter  Yellow. — The  di-methyl  derivative  of  amino  azo  benzene 
which  we  have  referred  to  in  our  discussion  of  the  general  method  for 
the  formation  of  amino  azo  compounds  by  the  Griess  reaction  (p.  569), 
is  also  a  dye  known  as  butter  yellow;  It  is  insoluble  in  water,  but  solu- 
ble in  oils  and,  therefore,  is  used  to  color  butter. 

Methyl  Orange. — Another  important  dye  compound  related  to  the 
above  is  the  well-known  methyl  orange  which,  though  not  used  as  a 
dye,  is  very  widely  used  as  an  indicator.  It  is  the  mono-sulphonate 
derivative  of  di-methyl  amino  azo  benzene.  The  alkali  salts  are 
orange  yellow  in  color  while  the  free  acid  is  red  violet,  and  these  are  the 
colors  obtained  when  the  indicator  is  used  in  acidimetric  titrations. 


574  ORGANIC  CHEMISTRY 

It  is  known  also  as  helianthine  and  as  tropaeolin  D.  It  is  not  prepared 
by  starting  with  amino  azo  benzene  but  with  sulphanilic  acid  which  is 
para-amino  benzene  sulphonic  acid.  This  is  diazotized  and  then 
coupled  with  di-methyl  aniline  yielding  the  azo  compound. 


HOS02—  C6H4—  NH2(p)  HOS02—  C6H4—  N2—  Cl 

Sulphanilic  acid  Diazo  compound  (salt) 

HOSO2—  C6H4—  N2(C1  +  H)C6H4—  N(CH3)2        -  > 

Di-methyl  aniline 

HOSO2—  C6H4—  N  =  N—  C6H4—  N(CH3)2 

para-Di-methyl  amino  azo  benzene  para  sulphonic  acid 
Methyl  orange 


X 
Di-amino  Azo  Benzene,  C6H6—  N  =  N—  C6H3\ 

NH2 

Both  di-amino  and  tri-amino  azo  compounds  are  known.  In 
these  compounds  in  which  two  amino  groups  are  in  the  same  ring  the 
azo  group  cannot  be  para  to  both  and  it  is  found  that  the  most  common 
form  is  the  one  in  which  one  amino  group  is  ortho  and  the  other  para. 


— N  =  N— /  >] 

NH2 

Di-amino  azo  benzene 


Chrysoidine.  —  The  hydrochloride  salt  of  this  compound  is  a  dye 
known  as  chrysoidine.  The  mono-hydrochloride  salt  is  yellow  while 
the  neutral  or  di-hydrochloride  salt  is  carmine.  The  free  base  crystal- 
lizes in  yellow  needles. 


/ 
Tri-amino  Azo  Benzene,  H2N—  C6H4—  N  =  N— 


NH2 


NH2 

The  important  tri-amino  azo  compound  is  the  one  in  which  two 
amino  groups  are  in  one  ring,  ortho  and  para  to  the  azo  group  and  one 
amino  group  meta  to  the  azo  group  in  the  other  ring.  The  constitution 
of  the  compound  is  proven  by  its  preparation  from  meta-phenylene 
di-amine,  meta-di-a,ndno  benzene.  This  is  diazotized  so  that  only  one 


INTERMEDIATE    NITROGEN   COMPOUNDS 


575 


of  the  amino  groups  is  diazotized  and   then  coupled  with  another 
molecule  of  the  rae/a-phenylene  diamine. 

(3)  (3) 


,NH2 

iH4V 

XN2(C1 


,NH2       diazotize 

XNH2 

(i) 

meta-Phenylene 
di-amine 

(3) 


C6H 


/ 


NH 


XN2— Cl 

(i) 

Di-azo  compound 

(3) 


NH2 
(i) 

meta-Phenylene 
di-amine 


N  =  N— 

(i)   (4) 


X 


Tri-amino  azo  benzene 


,NH2(3) 
NH2(i) 


When  the  diazotization  of  the  meta  phenylene  diamine  is  carried 
further  so  that  both  amino  groups  are  diazotized  a  double  diazo  com- 
pound or  tetrazo  compound  is  obtained  and  this  couples  with  two  mole- 
cules of  meta-phenylene  diamine  yielding  a  double  azo  or  dis-azo 
compound. 


NH2 

/    \ 

meta-Phenylene 
di-amine 


(3) 


C6H4! 


•N2- 

,  W 

Tetrazo  compound 


(3) 

;N2— (Cl    H)C6H3<( 

NH2 

(i) 

(3) 

im* 
(Cl    H)C6H3<( 

NH2 

(i) 

me  ta  -Phenylene 
di-amine  (2  mol.) 


N2—  Cl 

Tetrazo  compound 


(3)    (4) 


(3) 


3 
X 


C6H4 


NH 


(3) 


\N  =  N— C6H3<f 

(i)   (4)  XNH2 

(i) 

Bismark  Brown 
Dis-azo  compound 


576  ORGANIC  CHEMISTRY 

Bismarck  Brown. — The  dis-azo  compound  obtained  meta-di- 
amino  benzene  dis-azo  benzene  meta-di-amino  benzene  is  a  dye 
known  as  Bismark  brown,  though  the  dye  is  probably  a  mixture  of  the 
dis-azo  compound  and  tri-amino  azo  benzene.  With  the  exception  of 
aniline  yellow  or  amino  azo  benzene  it  was  the  first  azo  dye  to  be  made. 
It  was  first  prepared  by  Martius  in  1864,  and  first  made  as  a  dye  in  1866. 

HYDROXY  AZO  COMPOUNDS 

The  hydroxy  azo  compounds  are  wholly  analogous  to  the  amino 
azo  compounds  and  much  that  we  have  said  in  regard  to  the  latter 
applies  without  exception  to  the  former.  The  chief  difference  is  that 
due  to  the  different  character  of  the  substituting  group.  While 
the  amino  azo  compounds  are  basic,  due  to  the  amino  group,  and  form 
salts  with  acids;  the  hydroxy  azo  compounds  are  acid,  forming  salts 
with  bases.  The  acid  character  is  due  to  the  aromatic  hydroxyl 
group  which,  as  we  shall  presently  show,  is  strongly  acid.  In  general 
the  hydroxy  azo  compounds  are  yellow  or  brown  in  color  and  the  azo 
dyes  formed  from  the  simpler  hydroxy  azo  compounds  possess  the 
same  general  color  and  are  mostly  yellow,  orange  or  red  with  a  few 
blue  and  black  dyes.  While  many  of  the  first  azo  dyes  made  are 
amino  azo  compounds  it  is  interesting  that  now  the  hydroxy  azo  com- 
pounds are  far  more  important.  It  is  also  a  striking  fact  that  while 
many  of  the  amino  azo  dyes  are  derivatives  of  benzene  and  its  homo- 
logues  the  important  hydroxy  azo  dyes  are  not  derivatives  of  benzene 
or  its  homologues,  but  of  naphthalene  which  is  a  hydrocarbon  of  another 
class  and  which  will  be  studied  later.  The  consideration  of  the  dyes 
of  this  type  will,  therefore,  be  taken  up  in  connection  with  this  new 
class  of  hydrocarbons. 

Azo  Dyes. — Enough  has  been  said  in  the  preceding  discussion  of  the 
azo  compounds,  including  amino  azo  and  hydroxy  azo  derivatives  to 
indicate  their  importance  in  the  dyestuff  industry.  When  we  consider 
the  great  variety  of  derivatives  and  complicated  products  which  can  be 
made,  we  may  form  some  idea,  even  without  further  elaboration,  of 
the  importance  of  this  large  group  of  compounds  which  universally 
possess  strong  color,  usually  a  different  color  in  the  free  base  or  acid 
and  in  the  salt,  and  which  have  been  found  to  possess  the  peculiar 
character  necessary  to  their  use  in  dyeing  fabrics.  The  relation  be- 
tween chemical  constitution  and  the  property  of  color  and  of  dyeing 


INTERMEDIATE   NITROGEN   COMPOUNDS  577 

fabrics  will  not  be  considered  as  it  belongs  to  a  more  special  treatment 
of  dyes  as  a  class.  In  our  study  we  are  concerned  only  with  the  chemi- 
cal constitution  and  relationship  of  the  individual  chemical  compounds 

HYDRAZO  COMPOUNDS 

C6H5— NH 
Hydrazo  Benzene, 

C6H5— NH 

When  azo  benzene  is  reduced  or  when  the  reduction  of  nitro  benzene 
is  continued  beyond  the  stage  of  the  azo  compound  we  obtain  hydrazo 
benzene,  a  colorless  crystalline  solid,  m.p.  126°.  The  reduction  may 
be  accomplished  (i)  by  using  zinc  and  alcoholic  sodium  hydroxide,  (2) 
by  means  of  an  alcoholic  solution  of  ammonium  sulphide  or  (3)  electro- 
lytically  in  the  presence  of  an  alkali. 

C6H5— NO2  C6H5— N  C6H5— NH 

C6H5— N02  C6H5— N  C6H5— NH 

Nitro  benzene  Azo  benzene  Hydrazo  benzene 

The  characteristic  difference  in  the  constitution  of  azo  compounds 
and  hydrazo  compounds  is  that  in  the  azo  compounds  the  two  aromatic 
rings  are  linked  by  two  nitrogen  atoms  which  are  themselves  doubly 
linked  to  each  other;  while  in  the  hydrazo  compounds  the  nitrogen  atoms 
linking  the  two  rings  together  are  singly  linked  to  each  other,  the  re- 
maining valence  of  each  trivalent  nitrogen  being  satisfied  by  an  addi- 
tional hydrogen  atom.  Just  as  these  two  benzene  compounds  are 
successive  reduction  products  of  nitro  benzene  so  also,  as  they  yield 
aniline  on  further  reduction  (p.  537),  they  may  be  considered,  in  the 
reverse  order,  as  successive  oxidation  products  of  aniline.  Thus  the 
two  nitrogen  atoms  of  the  azo  compounds  and  the  two  (NH)  groups  of 
the  hydrazo  compounds  are  residues  of  amino  groups.  As  in  the  azo 
compounds  so  also  in  the  hydrazo  the  two  rings  may  be  alike  giving 
symmetrical  compounds,  or  they  may  be  unlike  giving  unsymmetrical. 

Oxidation  and  Reduction. — Hydrazo  compounds  are  usually  color- 
less crystalline  substances  insoluble  in  water,  but  soluble  in  alcohol. 
They  oxidize  easily,  even  in  the  air,  yielding  the  azo  compound,  and  on 
reduction  yield  the  amino  compound.  At  high  temperatures  they 
often  undergo  a  reciprocal  oxidation  and  reduction  of  two  molecules  one 
being  oxidized  at  the  expense  of  the  other  which  is  thereby  reduced, 

37 


ORGANIC  CHEMISTRY 

Thus  hydrazo  benzene  reacts  with  itself  and  yields  both  azo  benzene 
and  aniline. 

(+H2) 
C6H5— NH— NH— C6H5 ^CeHgNHs 

Aniline 

(-H2) 
C6H6— N=N— C6H6       C6H6— NH— NH— C6H6 

Azo  benzene  Hydrazo  benzene  • 

(2  mol.) 

Secondary  Amines. — Like  secondary  amines  the  hydrazo  compounds 
contain  the  (NH)  group  and  toward  nitrous  acid  hydrazo  benzene 
reacts  at  low  temperatures  in  the  manner  characteristic  of  this  class  of 
amines  (p.  61)  and  yields  a  double  nitroso  amine  compound. 

C6H5— N(H          HO)— NO  C6H5— N(NO) 

|          +  -»  |  +  2H20 

C6H5— N(H          HO)— NO  C6H5— N(NO 

Hydrazo  benzene  Nitroso  amine  compound 

Molecular  Rearrangement.— Like  several  of  the  other  nitrogen 
compounds  which  we  have  been  studying,  hydrazo  benzene  undergoes  a 
molecular  rearrangement  resulting  in  a  compound  in  which  the  two 
rings,  instead  of  being  linked  by  means  of  nitrogen  groups,  become 
directly  linked  to  each  other,  the  two  imino  nitrogen  groups  becoming 
two  amino  groups  in  the  para  position  to  the  linkage  of  the  rings. 

Benzidine. — The  compound  formed  is  known  as  benzidine,  and  is  a 
di-amino  derivative  of  a  hydrocarbon  consisting  of  two  benzene  rings 
directly  linked  together,  known  as  di-phenyl.  Both  of  these  will  be 
considered  later  (p.  730). 

C6H5— NH  C6H4— NH2(p) 


C6H5—  NH               C6H4—  NH2(p) 
or 
H        H                                  H        H 
C        C                                    C        C 
OA  ^ 

C—  NH—  NH—  C/ 
\_ 

VH 
/ 

C         C                                   C 
H        H                                   H 

C 
H 

Hydrazo  benzene 


INTERMEDIATE   NITROGEN   COMPOUNDS 


579 


H 
C 


H 
C 


H 
C 


H 
C 


H2N— 


C— C 


C— NH2 


C        C  C        C 

H        H  H        H 

Benzidine 
p-Di-amino  di-phenyl 

The  compound  formed  like  those  in  similar  rearrangements  is  the  para 
compound,  i.e.,  the  linking  of  the  rings  occurs  in  the  position  para  to 
the  amino  groups.  If,  in  the  case  of  derivatives  of  hydrazo  benzene, 
the  position  para  to  the  nitrogen  link  is  occupied  then  the  direct  linking 
of  the  rings  occurs  in  the  position  ortho  to  the  amino  groups.  The 
rearrangement  in  the  case  of  hydrazo  benzene  is  accomplished  by  simply 
boiling  with  mineral  acids. 

Benzidine  Dyes. — -The  importance  of  hydrazo  compounds  in  con- 
nection with  dyes  is  not  on  their  own  account  for,  as  has  been  stated, 
they  are  colorless  compounds;  but  because  they  are  easily  oxidized  to 
azo  compounds  which  are  dye  compounds  and  because  of  the  above 
rearrangement  into  compounds  like  benzidine  which  yield  dyes  known 
as  benzidine  dyes  (p.  787). 

HYDRAZINES 

Derivatives  of  Di-amide. — We  have  discussed  the  relationship  of 
hydrazo  benzene  to  aniline  and  just  as  aniline  is  a  derivative  of  one 
molecule  of  ammonia  so  hydrazo  benzene  may  be  considered  as  a 
derivative  of  two  molecules  of  ammonia  or  better  as  a  derivative  of 
di-amide  (p.  64),  which  is  itself  derived  from  two  molecules  of  ammo- 
nia by  the  substitution  of  an  amino  group  into  ammonia  itself. 
NH3  >  C6H5— NH2  C6H3— NH 


NH3 

Ammonia 
2  mol. 

NH, 


C6H5— NH2 

Aniline 

(primary  amine) 
2  mol. 

NH, 


C6H6—  NH 

Hydrazo  benzene 

(secondary  amine) 
i  mol. 

C6H6—  NH 


NH3 

Ammonia 


NH2 

Di-amide 

(primary  amine) 


C6H5—  NH 

Hydrazo  benzene 

(secondary  amine) 


580  ORGANIC  CHEMISTRY 

As  a  derivative  of  diamide,  however,  another  compound  is  more 
important  than  hydrazo  benzene.  This  is  known  as  phenyl  hydrazine, 
and  it  stands  intermediate  between  diamide  and  hydrazo  benzene. 
Just  as  dibasic  acids  form  not  only  neutral  salts  and  neutral  amides,  but 
also  acid  salts  and  acid  amides  by  the  replacement  of  one  acid  hydrogen 
by  a  metal  or  one  acid  hydroxyl  by  the  amino  group;  so  diamide  being 
a  di-amine  yields  not  only  derivatives  in  which  the  two  amino  groups 
each  have  a  hydrogen  replaced  by  a  radical  but  also  intermediate 
compounds  resulting  from  the  substitution  of  a  hydrogen  in  only  one 
amino  group.  Such  an  intermediate  phenyl  derivative  of  di -amide 
we  shall  now  study.  As  diamide  is  known  also  as  hydrazine  its  phenyl 
derivative  is  known  as  phenyl  hydrazine. 

NH2  C6H5— NH  C6H5— NH 

NH2  NH2  C6H5— NH 

Diamide  Phenyl  Hydrazo  benzene 

hydrazine  hydrazine        Di-phenyl  hydrazine 

Hydrazines.— It  will  readily  be  seen  that  these  two  compounds  are 
not  the  only  aromatic  (aryl)  derivatives  of  di-amide  or  hydrazine.  The 
following  series  is  possible;  the  aryl  radical,  when  more  than  one  is 
present  being  either  like  or  different. 

NH2  Ar— NH  Ar— NH 


NH2                        NH2  Ar— NH 

Hydrazine               Mono-hydrazines  Sym.  Di-hydrazines 

Phenyl  hydrazine  Hydrazo  benzene 

Ar2  =  N                    Ar2  =  N  Ar2  =  N 


NH2  Ar— NH  Ar2  =  N 

Unsym.  Tri-hydrazines         Tetra-hydrazines 

Di-hydrazines 

All  of  these  compounds  are  termed  hydrazines  although  the  symmetri- 
cal di-hydrazines  retain  the  name  of  hydrazo  compounds  because  of 
their  relationship  to  the  azo  compounds. 

Phenyl  Hydrazine,  C6H5— NH— NH2 

Phenyl  hydrazine  is  by  far  the  most  important  of  the  hydrazine 
compounds.  It  is  a  colorless  oil  readily  becoming  dark  colored.  It 
melts  at  17.5°  and  boils  at  243.5°.  It  forms  a  crystalline  hydrate, 
m.p.  24.1°,  with  1/2  mol.  H2O,  C6H5— NH— NH2  i/2H2O.  As  it 


INTERMEDIATE   NITROGEN   COMPOUNDS  581 

contains  a  primary  amine  group  it  possesses  basic  properties  yielding 
soluble  crystalline  salts,  e.g.,  C6H5  —  NH  —  NH2.HC1,  phenyl  hydrazine 
hydrochloride. 

Carbohydrate  Reagent.  —  The  importance  of  phenyl  hydrazine 
rests  upon  its  use  as  a  reagent  in  the  study  of  the  carbohydrates  and 
other  aldehyde  or  ketone  compounds.  The  reaction,  together  with  the 
analogous  one  of  hydroxyl  amine,  has  been  fully  discussed  in  Part  I, 
p.  326,  but  may  be  repeated  in  this  connection.  It  is  based  upon  the 

characteristic  property  of  the  carbonyl  group,  —  C  =  O,  in  aldehydes  and 
ketones  to  react  with  an  amino  group  containing  two  unsubstituted 
hydrogen  atoms. 

H  H 

I 
R—  C  =  (O  +  H2)N—  OH  —  >        R—  C  =  N—  OH  +  H2O 

Aldehyde  Hydroxyl  amine  An  Ald-oxime 

R  R 

R—  C  =  (O  +  H2)N—  NH—  C6H5  -  >  R—  C  =  N—  NH—  C6H6+H2O 

Ketone  Phenyl  hydrazine  A  Phenyl  hydrazone 

The  products  are  known  as  oximes,  from  hydroxyl  amine  and  hydra- 
zones  from  the  hydrazine.  Phenyl  hydrazine  yields  phenyl  hydrazones 
of  the  particular  aldehyde  or  ketone  with  which  it  reacts.  The  reac- 
tion is  of  value  in  connection  with  the  carbohydrates  because  these 
react  as  aldehyde  or  ketone  compounds  and  because  the  hydrazones 
formed  undergo  further  reaction  with  phenyl  hydrazine. 

Oxidizing  Agent.  —  This  subsequent  reaction  with  phenyl  hydrazine 
is  due  to  its  action  as  an  oxidizing  agent.  If  the  reduction  of  the  phenyl 
hydrazine  is  brought  about  by  hydrogen,  zinc  and  hydrochloric  acid, 
the  products  are  aniline  and  ammonia. 

C6H5—  NH—  NH2  +  H2    -  >    C6H5—  NH2  +  NH3 

Phenyl  hydrazine  Aniline 

This  'same  reduction  of  phenyl  hydrazine  occurs  when  it  acts  as  an 
oxidizing  agent  upon  the  hydrazone  formed  by  the  reaction  between 
glucose  and  phenyl  hydrazine. 


CH2—  OH—  (CH—  OH)3—  CH—  OH^CH  =  (O  +  H2)N—  NH—  C6H5 

Glucose 

-»          CH2OH—  (CH—  OH)3—  CH—  OH—  CH  =  N—  NH—  C6H5 

Glucose  phenyl  hydrazone 


582        .  ORGANIC  CHEMISTRY 

On  this  glucose  phenyl  hydrazone  the  phenyl  hydrazine  acts  as  an 
oxidizer  and  one  of  the  secondary  alcohol  groups  (  — CH — OH — )  is 
oxidized  to  a  ketone  carbonyl  group,  the  phenyl  hydrazine  being  reduced 
as  above  to  aniline  and  ammonia. 

CH2— OH— (CH— OH)3— CH— OH— CH  =  N— NH— C6H5  + 

Glucose  phenyl  hydrazone 

C6H6— NH— NH2    > 

Phenyl  hydrazine 

CH2— OH—  (CH— OH)  3— C— CH  =  N— NH— C6H5 

O 

Intermediate  product 

+  C6H5— NH2  +  NH3 

Aniline 

Osazones. — The  intermediate  product  thus  formed  containing  now  a 
carbonyl  group  reacts  with  a  third  molecule  of  phenyl  hydrazine  form- 
ing a  di-hydrazone  which  is  termed  an  osazone. 

CH2— OH— (CH— OH)3— C— CH  =  N— NH— C6H5 

II  — 

(O  +  H2)N— NH— C6H5 

CH2OH—  (CH— OH)  3— C— CH  =  N— NH— C8H5 
N— NH— C6H6 

Glucosazone 

(An  osazone) 

The  osazones  are  crystalline  products  able  to  be  separated  and 
identified,  and  furthermore  by  hydrolysis  they  split  off  both  phenyl 
hydrazine  radicals  yielding  an  aldehyde-ketone  product  of  the  original 
glucose  known  as  an  osone,  i.e.,  glucosone.  This  by  reduction  yields 
the  ketone  sugar  corresponding  to  the  original  aldehyde  sugar  with 
which  we  started  (p.  328). 

Reducing  Agent. — Phenyl  hydrazine  may  also  act  as  a  reducing 
agent.  Nitro  and  nitroso  compounds  are  reduced  by  it  to  am ino  com- 
pounds the  phenyl  hydrazine  being  oxidized  to  benzene.  Phenyl 
hydrazine  also  yields  benzene  when  oxidized  by  ferric  choride  or  Feh- 
ling's  solution,  the  nitrogen  being  set  free  quantitatively  thus  giving  a 
means  of  determining  the  amount  of  hydrazine  present. 

C6HB— NH— NH2  +  O  — »        CeH6  +  N2  +  H2O 

Phenyl  hydrazine  Benzene 


INTERMEDIATE   NITROGEN   COMPOUNDS  583 

By  more  cautious  oxidation  with  mercuric  oxide,  copper  sulphate  or 
ferric  chloride,  the  salts  of  phenyl  hydrazine  yield  salts  of  diazo  benzene. 

C6H5—  NH—  NH2.HC1  +  O2        -  >        C6H6—  N2—  Cl  +  2H2O 

Phenyl  hydrazine  Benzene  diazonium 

salt  chloride 

Conversely  benzene  diazonium  chloride  by  reduction  with  zinc  and 
acetic  acid  yields  phenyl  hydrazine. 

Tri-azo  Compounds.  —  As  phenyl  hydrazine  is  both  a  primary  and  a 
secondary  amine  the  (NH)  group  reacts  with  nitrous  acid  yielding  a 
nitroso  amine  compound.  This  compound  is  very  unstable,  readily 
losing  water,  and  forming  a  compound  in  which  the  ring  is  linked  to  a 
three  nitrogen  group.  It  is  known  consequently  as  a  tri-azo  compound, 
also  as  a  diazo  imide. 
C6H5—  N(H)—  NH2  +  HO)—  NO  -  >  C6H5—  N(NO)—  NH2 

Phenyl  hydrazine  Nitroso  amine  compound 

-HO  N 

C6H6—  N—  N(H2        _!r         C6H6— 


•i^-  //-\  Tri-azo  compound 

This  triazo  compound  is  a  derivative  of  the  interesting  nitrogen-hydrogen 
acid,  N3H,  hydrazoic  or  triazoic  acid,  (p.  64). 

Derivatives.  —  Pour  classes  of  derivatives  of  phenyl  hydrazine  are 
known;  (i)  Those  containing  hydrocarbon  radicals  in  place  of  amino 
hydrogen  atoms, 

C6H5—  N—  CH3        alpha-Methyl  phenyl  hydrazine 

NH2 
C6HB—  NH  beta-Methyl  phenyl  hydrazine 

I 

CH3—  NH 
C6H5—  N—  CH3        Tri-methyl  phenyl  hydrazine 

I 
CH3—  N—  CH3 

These  correspond  to  the  di-,  tri-,  and  tetra-hydrazines  previously 
mentioned.  (2)  Derivatives  containing  a  substituting  group  in  the 
ring,  e.g.; 

/NH—  NH2 

C6H4<  Phenyl  hydrazine  sulphonic  acid 

\S02OH 


584  ORGANIC  CHEMISTRY 

(3)  Derivatives  of  the  acid  amide  type  in  which  phenyl  hydrazine,  as 
an  amine,  reacts  with  carboxyl  acids  or  acid  chlorides. 

C6H5— NH— NH(H+HO)OC—CH3 — »C6H5— NH  —  NH— OC— CH3 

Phenyl  hydrazine  Acetic  acid  Acetyl  phenyl  hydrazine 

Phenyl  acet  hydrazide 

These  products  are  termed  hydrazides. 

(4)  Derivatives  of  the  ammo  acid  type  in  which  phenyl  hydrazine, 
as  an  amine,  is  substituted  for  a  hydrogen  atom  of  the  hydrocarbon 
radical  of  an  acid.  They  are  known  as  hydrazino  acids,  e.g.; 

C6H5-NH— NH— CH2— COOH    Phenyl  hydrazino  acetic  acid 
In  both  of  the  last  two  derivatives  either  one  of  the  primary  or  the 
secondary  amine  hydrogen  may  be  replaced. 


VI.  DI-AZO  COMPOUNDS. 

In  the  preceding  discussion  of  the  aromatic  nitrogen  compounds  we 
have  repeatedly  referred  to  the  diazo  compounds  and  to  certain  reac- 
tions which  they  undergo  especially  those  by  which  they  yield  azo 
compounds  (p.  569).  The  general  formula  for  diazo  compounds, 
R — N2 — X,  differs  from  those  for  azo  compounds,  R — N  =  N — R,  and 
hydrazo  compounds,  R — NH — NH— R,  in  that  only  one  of  the  two 
nitrogen  atoms  is  linked  directly  to  a  ring.  The  number  of  atoms  of 
nitrogen  in  proportion  to  one  aromatic  ring  being  two,  whereas  in  azo 
compounds  it  is  one,  explains  the  name  di-azo. 

The  diazo  compounds  are  characterized  also  by  their  great  in- 
stability which  is  evident  in  the  explosive  nature  of  the  dry  salts  and 
in  the  great  ease  with  which  they  undergo  reaction  when  in  solution. 
It  is  this  last  fact  which  enables  them  to  be  used  in  the  laboratory  and 
in  industrial  operations  for  the  preparation  of  many  valuable  com- 
pounds, especially  dyes.  No  class  of  compounds  in  the  whole  field  of 
organic  chemistry  has  been  so  rich  in  the  yield  of  important  products, 
or  so  widely  applicable  as  a  means,  either  direct  or  indirect,  of  bringing 
about  certain  desired  results.  Their  discovery  is  one  of  the  important 
landmarks  in  the  history  of  organic  chemistry  and  the  developments 
resulting  from  it  both  in  the  science  of  chemistry  and  in  the  industries 
have  been  comparable  with  those  resulting  from  the  discovery  of  the 
mother  substance  coal  tar. 

Diazo  compounds  are  soluble  in  water,  but  practically  insoluble  in 
alcohol  or  ether.  On  account  of  their  explosive  nature  when  dry  they 
are  seldom  obtained  in  any  amount  as  the  pure  dry  product.  When 
necessary  to  isolate  the  pure  compound,  only  very  small  quantities, 
o.i  to  0.2  g.  are  ever  separated.  It  is  usually  unnecessary  to  isolate 
the  compounds  as  such,  as  they  are  simply  intermediate  steps  in  the 
preparation  of  other  compounds  resulting  from  their  decomposition  by 
different  reagents.  Therefore  they  are  held  in  the  solution  in  which 
they  are  prepared  and  decomposed  at  once.  Details  in  regard  to 
amount  of  reagent  used,  the  regulation  of  the  temperature  during  the 
reaction,  thorough  stirring,  etc.,  must  oftentimes  be  carefully  observed 

585 


586  ORGANIC  CHEMISTRY 

if  successful  results  are  to  be  obtained.  These  will  not  be  taken  up 
here,  but  may  be  found  in  descriptions  of  laboratory  methods  for 
special  cases.  The  study  and  use  of  these  exceedingly  unstable  com- 
pounds has  shown  in  a  remarkable  way  the  difficulties  and  triumphs  of 
laboratory  and  industrial  technique. 

Peter  Griess,  1858. — Diazo  compounds  were  discovered  and  first 
prepared  by  Peter  Griess  in  1858.  The  historical  method  used  by 
him  is  the  same  in  general  as  is  now  used  widely  in  dyestuff  manufac- 
ture. It  has  already  been  described  and  consists  in  the  action  of 
nitrous  acid  on  an  aromatic  primary  amine,  e.g.,  aniline.  When  this 
reaction  takes  place,  at  ordinary  or  slightly  raised  temperatures,  the 
same  products  are  obtained  as  with  aliphatic  primary  amines,  viz., 
the  hydroxyl  compound  of  the  hydrocarbon  radical,  free  nitrogen  and 
water. 

C6H6-i-N=!-H2    Aniline  C6H5— OH   +N2+H2O 

HO— j— N=;=O      Nitrous  acid       Hydroxy  benzene 

When,  however,  the  reaction  takes  place  in  the  cold  an  aromatic  amine 
yields  the  intermediate  diazo  compound. 

C6H6— N--H2        Aniline  C6H5— N2— OH+H2O 

HO — N=  =O         Nitrous  acid  Diazo  benzene 

The  details  of  this  reaction  and  the  one  following  will  be  considered 
later  in  duscussing  the  constitution  of  diazo  compounds.  The  reaction 
always  takes  place  in  an  acid  solution,  i.e.,  with  the  salt  of  the  amine,  so 
that  the  product  obtained  is  not  the  diazo  benzene  as  written  above, 
but  the  salt  of  it. 

C6H6— NH2.HC1  +  HO— NO        >        C6H5— N2— Cl  +  2H2O 

Aniline  Benzene  diazonium 

chloride 

Diazotization. — The  reaction  is  termed  diazotization,  i.e.,  we  diazo- 
tize  the  amine.  These  terms  are  now  of  every-day  use  in  the  synthesis 
of  organic  compounds  and  are  similar  and  almost  as  familiar  as  the 
terms  oxidation  and  oxidize.  While  the  principle  of  diazotization 
and  the  general  reaction  is  as  given  above  there  are  various  modifica- 
tions that  have  been  introduced.  Originally  the  nitrous  acid  for  the 
diazotization  was  prepared  in  the  presence  of  the  amine  by  passing 


DIAZO   COMPOUNDS  587 

nitrogen  trioxide  gas,  N2O3,  into  the  water  solution  of  the  amine  salt, 
the  nitrogen  trioxide  being  prepared  by  the  action  of  arsenious  oxide, 
As2Os,  upon  nitric  acid.  At  present  this  proceedure  is  rarely  followed; 
but  instead  sodium  nitrite,  NaNO2,  is  added  to  an  acid  solution  of  the 
amine  salt.  In  both  cases  the  diazo  compound  is  obtained  as  a  water 
solution  of  the  diazonium  salt  which  must  usually  be  kept  cold  in  order 
to  prevent  decomposition.  If  it  is  desired  to  obtain  the  diazonium 
salt  as  a  crystalline  product  in  alcohol,  then,  instead  of  sodium  nitrite, 
we  use  either  amyl  nitrite,  (CH3)2  =  CH—  CH2—  CH2—  NO2,  or  ethyl 
nitrite,  C2H5  —  NO2  (p.  104).  These  nitrites  with  acids  yield  nitrous 
acid.  The  result  then  of  all  of  the  proceedures  for  diazotization  is  the 
bringing  together  oifree  nitrous  acid  and  the  salt  of  an  aromatic  primary 
amine,  the  reaction  between  these  two  taking  place  as  described.  It  is 
considered  probable  by  some  that  the  diazo  reaction  takes  place  in 
two  steps,  first,  the  formation  of  a  nitroso  amine  compound,  as  in  the 
case  of  secondary  amines  with  nitrous  acid  and,  second,  the  rearrange- 
ment of  this  nitroso  amine  into  the  diazo  compound. 

C6H6—  NH(H  +  HO)—  NO        -  >        C6H5—  NH—  NO  +  H2O 

Aniline  Phenyl  nitroso 

amine 

rearrangement 
C6H6—  NH—  NO  —  *         C6H6—  N2—  OH 


Phenyl  nitroso  amine  Diazo  benzene 

Diazo  compounds  may  also  be  prepared  from  hydrazines  by  cautious 
oxidation  with  mercuric  oxide,  copper  sulphate  or  ferric  chloride 
(p.  583)- 

+02 
C6H5—  NH—  NH2    ;m:    C6H5—  N2—  OH+H2O 

Phenyl  hydrazme  4-oTT  Diazo  benzene 

The  reverse  reaction  also  takes  place  on  reduction  if  the  diazonium 
salt,  usually  the  sulphite,  is  reduced  by  means  of  zinc  and  acetic  acid. 

Diazo  Benzene,  C6H6—  N2—  OH 
Benzene  Diazonium  Chloride,  CeH5  —  Na  —  Cl 

Constitution.  —  In  the  following  discussion  of  the  constitution  and 
reactions  of  diazo  compounds  diazo  benzene  and  its  salts  will  be  taken 
as  examples.  The  reactions,  however,  are  to  be  considered  as  typical 
of  all  diazo  compounds.  The  physical  properties  of  free  diazo  com- 


588  ORGANIC  CHEMISTRY 

pounds  are  known  in  only  a  few  cases  because  the  study  of  them  is 
attended  with  both  difficulties  and  dangers.  Diazo  benzene,  to  which 
we  give  the  formula  C6H5 — N2  —  OH,  has  never  been  obtained  as  such. 
It  is  formed  in  solution  when  moist  silver  oxide  acts  upon  the  chloride 
salt  of  diazo  benzene.  It  acts  as  a  base  but  rapidly  decomposes. 

Bases,  Neutral  Salts. — As  a  base  it  forms  salts,  in  which  form  the 
diazo  compound  is  obtained  by  diazotization,  and  which  though  also 
unstable  has  been  isolated  in  small  quantities  and  the  composition  and 
properties  determined.  Of  the  three  salts,  the  sulphate,  chloride  and 
nitrate,  the  first  is  the  most  stable  and  the  last  is  the  least  stable. 
They  are  colorless  crystalline  neutral  compounds  soluble  in  water, 
difficultly  soluble  in  alcohol  and  insoluble  in  ether.  After  being  pre- 
pared by  the  ordinary  diazo  reaction,  with  sodium  nitrite  in  cold  acid 
water  solution,  they  may  be  precipitated  in  crystalline  form  by  the 
addition  of  alcohol  and  ether.  If  the  diazotization  is  effected  in  alcohol 
solution  by  means  of  amyl  nitrite  or  ethyl  nitrite  the  crystals  of  the 
diazonium  salt  separate  at  once.  These  salts  of  diazo  benzene  all 
show  true  salt  characteristics,  e.g.,  they  lower  the  freezing  point  of 
solutions.  The  diazo  radical,  (C6H5 — N2 — )  is  thus  basic  toward 
strong  acids,  and  the  hydroxide,  the  non-isolated  hypothetical  diazo 
benzene,  C6H5 — N2 — OH,  is  the  free  base.  It  may  be  considered  as 
the  simplest  aromatic  diazo  compound  and  the  mother  substance  of  all 
other  members  of  the  class. 

What  now  is  the  constitution  of  these  diazo  compounds?  The 
facts  thus  far  considered  and  which  must  be  explained  by  an  accepted 
constitutional  formula  are,  (i)  Their  formation  by  the  action  of  nitrous 
acid  on  a  primary,  amine,  (2)  Their  conversion  into  azo,  amino  azo, 
hydroxy  azo  and  hydrazine  compounds  and  (3)  the  basic  character  of 
the  hydroxy  compound,  diazo  benzene,  and  the  true  salt  character  of 
the  compounds  formed  with  strong  acids. 

Griess  Formula. — Historically  interesting  is  the  first  formula  pro- 
posed by  Griess.  Because  of  the  ammonium  salt-like  character  of  the 
salts  of  diazo  compounds  he  assumed  that  the  formula  for  benzene 

v    /H 
diazonium  chloride  was,  C6H4 — N"'  =  N\       ,  one  of  the  nitrogen  atoms 


being    pentavalent    as    in    ammonium    chloride.     In    this    formula 
each  nitrogen  is  linked  to  the  ring,  a  condition  which  was  disproved  by 


DIAZO   COMPOUNDS  589 

the  fact  that  a  tetra-brom  sulphonic  acid  derivative  of  aniline  yields  a 
diazo  compound  in  which  the  four  bromine  atoms  and  the  one  sulphonic 
acid  group  remain  unchanged;  the  diazo  nitrogen  group  being  thus 
attached  to  the  ring  at  one  point  only,  where  the  original  amine  group 
was  situated.  This  was  also  supported  by  the  fact  that  in  azo  com- 
pounds, which  are  readily  formed  from  the  diazo,  only  one  nitrogen  is 
linked  to  the  original  benzene  ring.  This  is  proven  by  the  decomposi- 
tion of  di-methyl  amino  azo  benzene,  formed  from  benzene  diazonium 
chloride  and  di-methyl  aniline,  which  on  reduction  splits  into  aniline 
and  para  amino  di-methyl  aniline. 

C6H5— N2(C1  +  H)— C6H4— N(CH3)2    > 

Benzene  diazonium  Di-methyl 

chloride  aniline 

C6H5— N  =  N— C6H4— N(CH3)2 

Di-methyl  amino 
azo  benzene 

+  H 
C6H5— N  =  N— C6H4— N(CH3)2 

Di-methyl  amino  azo 
benzene 

CeH— NH2  +  H2N— C6H4— N(CH3)2 

Aniline  para-Amino    di-methyl 

aniline 

The  idea  that  the  diazo  nitrogen  group  is  attached  to  the  ring  by  only 
one  nitrogen  and  at  only  one  point  is  further  supported  by  many  of  the 
reactions  of  diazo  compounds  which  result  in  the  replacement  of  both 
of  the  nitrogen  atoms  by  one  element  or  group  linked  to  the  ring  at 
only  one  point,  and  this  is  in  the  position  originally  occupied  by  the 
amino  radical  of  the  primary  amine  from  which  the  diazo  compound 
was  formed. 

Kekule  Formula. — These  facts  led  Kekule  to  suggest  a  second  for- 
mula in  which  the  nitrogen  atoms  are  both  trivalent  and  in  the  same 
relationship  to  each  other  and  the  ring  as  they  are  in  azo  benzene.  The 
formula  is  C6H5 — N  =  N — Cl,  benzene  diazonium  chloride.  For 
some  time  this  was  the  accepted  formula;  for,  if  we  put  it  in  the  reac- 
tions which  we  have  written  for  the  formation  of  diazo  compounds  and 
for  their  conversion  into  azo  compounds  and  into  hydrazines,  we  find 
that  it  is  satisfactory.  It  does  not  agree,  however,  with  the  true  salt 
character  of  benzene  diazonium  chloride  nor  the  strongly  basic  nature 
of  the  hydroxide  compound,  the  free  diazo  benzene.  In  every  respect 
the  neutral  salts,  e.g.,  benzene  diazonium  chloride  and  the  free  diazo 


590  ORGANIC  CHEMISTRY 

base,  resemble  ammonium  salts  and  ammonium  hydroxide.  As  in 
these  latter  compounds  nitrogen  is  pentavalent  so  in  the  diazo  salts 
and  base  one  nitrogen  atom,  evidently  the  original  amino  nitrogen, 
must  be  pentavalent.  This  was  partially  accounted  for  in  the  original 
Griess  formula  but  this  we  have  seen  is  not  in  agreement  with  facts. 

Bloomstrand,  Strecker  and  Erlenmeyer  Formula. — These  ideas 
resulted  in  the  suggestion  of  a  formula  known  as  the  Bloomstrand  - 
Strecker-Erlenmeyer  formula  for  the  salts  and  the  free  base  which  is  as 
follows: 

C6N5— N— Cl 

HI  Benzene  diazonmm  chloride 

j|}  (Salt) 

C6H5— N— OH 

HI  Benzene  diazonmm  hydroxide 

Ijj  (Free  base) 

Bloomstrand-Strecker-Erlenmeyer  formulas. 

This  new  formula  agrees  better  with  the  formation  of  diazo  compounds, 
for  in  diazotizing  it  is  always  necessary  to  use,  not  the  free  amine,  but 
the  salt  of  the  amine.  The  Kekule  formula  fits  the  case  only  if  the 
reaction  is  written  with  the  amine  itself.  If,  however,  we  write  the 
reaction  with  the  ammonium-like  salt  of  the  amine  we  find  that  an 
ammonium-like  salt  will  naturally  result  thus  agreeing  with  the  facts. 

v  v 

C6HB— N— Cl      Aniline  hydrochloride      C6H6— N— Cl 

/l\  III 

(H)  (HH)       +  N'" 

(HO)— N"'  =  (O)     Nitrous  acid  Benzene  diazonium 

chloride 

Such  a  reaction  agrees  perfectly  with  the  new  formula  which  has  been 
generally  accepted  as  expressing  the  constitution  of  the  free  diazo 
base  and  the  salts.  The  base  thus  takes  the  name  benzene  diazonium 
hydroxide  and  the  salts,  e.g.,  the  chloride,  benzene  diazonium  chloride 
signifying  their  ammonium  character.  The  new  formula  does  not, 
however,  fit  the  reactions  by  which  diazo.  compounds  are  converted 
into  azo  or  amino  azo  compounds  nor  the  reduction  of  diazo  benzene  to 
phenyl  hydrazine.  Thus  we  have  two  formulas  neither  of  which 


DIAZO   COMPOUNDS 


591 


explains  all  of  the  three  sets  of  facts  mentioned  (p.  588),  but  both  of 
which  explain  two  of  them. 

Tautomerism. — We  have  evidently  then  another  example  of  tauto- 
merism  as  both  formulas  are  necessary  in  order  to  explain  the  facts 
and  both  are  true  under  certain  conditions.  This  has  been  well  sup- 
ported by  some  additional  facts  which  favor  the  Kekule  formula,  but 
which  also  show  that  both  formulas  must  be  true. 

Acids,  Alkali  Salts. — The  free  diazo  benzene  base  which  will  always 
be  spoken  of  now  as  benzene  diazonium  hydroxide  and  which  necessi- 
tates the  introduction  of  the  pentavalent  nitrogen  formula  is  formed 
by  the  action  of  silver  hydroxide  upon  benzene  diazonium  chloride. 
By  the  action  of  acids  the  diazonium  hydroxide  is  converted  into  salts 
and  these  salts  are  neutral.  If,  however,  the  diazonium  chloride  is 
treated  with  alkalies,  like  potassium  hydroxide,  we  obtain  alkali  metal 
salts  of  the  diazo  compound. 

Diazotates.  Isomerism. — These  salts  are  called  diazotates,  are 
alkaline,  and  are  not  quite  so  unstable  as  the  neutral  diazonium  salts. 
They  are  crystalline  compounds,  soluble  in  water  and  alcohol,  but 
insoluble  in  ether.  By  the  action  of  acids  they  yield  the  neutral  dia- 
zonium salts.  Again,  if  a  hot  strong  alkaline  solution  is  used  an  iso- 
meric  salt  called  an  iso-diazotate  is  obtained  which  is  a  stable  compound. 
According  to  our  ideas  it  is  impossible  to  conceive  of  a  compound  of  the 
constitution  of  the  diazonium  hydroxide,  like  ammonium  hydroxide, 
which  is  acid  in  character.  There  must  then  be  two  hydroxide 
compounds  of  diazo  benzene:  benzene  diazonium  hydroxide,  a  penta- 
valent nitrogen  base,  and  a  'tautomeric  compound  which  is  called 
benzene  diazo  hydroxide,  and  which  is  acid  in  character.  The  two 
are  transformable  into  each  other  under  conditions  usually  effecting 
tautomeric  change.  The  diazonium  compounds  agree  with  the  Bloom- 
strand -Strecker-Erlenmeyer  formula.  The  benzene  diazo  hydroxide 
should  then  agree  with  the  tautomeric  Kekule  trivalent  nitrogen 
formula.  Does  this  formula,  however,  fit  the  case  of  the  isomerism 
of  the  diazo tates  which  we  have  mentioned? 

Hantzsch  Stereo  Formula. — A  development  of  the  Kekule  formula 
to  agree  with  the  existence  of  isomeric  diazotates  was  suggested  by 
Hantzsch.  He  assumed  geometric  stereo-isomerism,  due  to  the  double 
linking  of  two  nitrogen  atoms,  and  this  assumption  has  been  supported 
not  only  by  the  isomerism  of  the  diazotates,  but  also  of  other  similar 


5Q2  ORGANIC  CHEMISTRY 

nitrogen  compounds.     The  Kekule  formula   then  as   developed  by 
Hantzsch  for  the  two  isomeric  potassium  diazotates  is : 
C6H5— N  C6H5— N 

II  II 

KO— N  N— OK 

Potassium  diazotate  Potassium  iso-diazotate 

Syn  form  Anti  form 

Unstable  ("labil")  Stable  ("stabil") 

Kekule -Hantzsch  formulas 

Syn.  Anti. — This  isomerism  is  geometric,  as  the  double  link  of  the 
two  nitrogen  atoms  prevents  free  rotation  and  the  structure  of  each 
form  will  remain  fixed.  The  two  forms  are  termed  syn  when  the  ring 
and  the  other  group  are  on  the  same  side  of  the  nitrogen  atoms  and 
anti  when  they  are  on  opposite  sides.  The  condition  is  exactly  analo- 
gous to  that  in  maleic  acid  and  fumaric  acid  in  which  two  carbon  atoms 
are  similarly  doubly  linked.  The  terms  syn  and  anti,  for  the  diazo- 
tates, are  analogous  to  cis  and  trans  for  maleic  and  fumaric  acids. 
H— C— COOH  H— C— COOH 

II  II 

H— C— COOH  HOOC— C— H 

Maleic  acid  Fumaric  acid 

Cis  form  Trans  form 

The  syn  form  being  the  more  unstable  represents  the  unstable  diazotate, 
while  the  anti  form  is  the  iso-diazotate,  the  stable  compound. 

Phenyl  Nitroso  Amine. — The  iso-diazotate  differs  in  a  noticeable 
way  from  the  diazotate.  Not  only  is  it  more  stable,  but  on  treatment 
with  acids  it  does  not  yield  diazonium  salts,  but  an  entirely  different 
compound,  viz.,  phenyl  nitroso  amine,  C6H5 — :NH — NO.  This  com- 
pound has  the  same  composition  as  the  diazo  hydroxide  and  the  rela- 
tionship means  that  the  isomeric  diazo  hydroxide  undergoes  structural 
rearrangement  into  a  new  compound.  This  is  the  reason  for  the  view 
that  this  same  compound,  phenyl  nitroso  amine,  is  an  intermediate 
product  in  the  formation  of  diazo  compounds  as  already  referred  to 
(p.  587).  These  relationships  may  be  shown  as  follows: 

-(H) 

/ 
C6H5— N       +  HC1      C6H5— N— Cl       -KOH      C6H5— N— Cl 

II         ^=^  II  ^=-  III 

KO— N       -HC1       (KO)— N  +KOH  N 

Potassium  diazotate  Intermediate  Benzene  diazonium 

addition  chloride 

product 


DIAZO   COMPOUNDS 


593 


C6H6— N  C6H5— N          rearrange-        C6H5— NH 

II  +HC1  ||  -->  | 
N— OK                                 N— OH    ment                        N  =  O 

Potassium  Benzene  iso-diazo  Phenyl  nitroso 

iso-diazotate  hydroxide  amine 

The  formation  of  the  diazotate  from  the  diazonium  salt  by  means  of 
alkalies  is  explained  by  the  reverse  of  the  first  reaction.  This  makes 
clear  the  reaction  by  which  the  diazonium  salts  yield  azo  compounds 
(p.  569).  The  reaction  takes  place  best  in  neutral  or  alkaline  solution 
and  under  these  conditions  the  diazonium  salt  would  yield  the  diazo 
hydroxide  compound  which  would  then  couple  with  the  amine  and 
form  the  amino  azo  compound. 

C6H5— N— Cl  N— C6H5 

III  +KOH       -+    ||  — * 
N                                     N— (OH  +  H)— C6H4— N(CH3)2 

Benzene  Benzene  Di-methyl 

diazonium  diazo  aniline 

chloride  hydroxide 

N— C6H5 

N— C6H4— N(CH3)2 

Di-methyl 

amino 
azo  benzene 

Benzene  Diazo  Sulphonic  Acid. — We  should  mention  here  another 
compound  which  seems  to  present  a  case  of  isomerism  like  that  of  the 
diazotates.  When  benzene  diazonium  chloride  is  treated  in  cold 
alkaline  solution  with  potassium  sulphite  the  following  empirical 
reaction  occurs: 

C6H5— N2— Cl  +  K2SO3  — >        C6H5— N2— SO3K  +  KC1 

This  compound  is  very  unstable  and  explosive  and  forms  hydroxy 
azo  compounds  by  coupling  with  hydroxy  compounds.  Furthermore, 
it  gives  sulphur  dioxide  when  treated  with  dilute  acids  just  as  sulphite 
salts  do.  It  appears,  therefore,  that  this  compound  is  a  true  diaz- 
onium compound,  viz.,  a  diazonium  sulphite,  and  the  reaction  should  be 

C6H5— N— Cl  +  KOSO2K        >        CbH6— N— OS02K 


N  N 

Benzene  Benzene  diazonium 

diazonium  potassium  sulphite 

chloride 

38 


594  ORGANIC  CHEMISTRY 

Now  this  unstable  compound  readily  changes  in  solution  into  a  stable 
form  and  this  new  compound  does  not  act  like  a  sulphite  and  yield 
sulphur  dioxide  with  acids,  but  by  reduction  it  yields  the  sulphonic 
acid  derivative  of  phenyl  hydrazine.  It,  therefore  is  a  true  sulphonic 
acid  derivative  of  the  diazotate  form,  viz., 

C6H6— N 

II 

N— SO2OK 

Benzene  diazo 
potassium  sulphonate 

Hantzsch  assigns  the  syn  and  anti  isomeric  formulas  for  the  above 
two  compounds  but  their  distinctly  different  properties,  one  a  sulphite 
the  other  a  sulphonic  acid,  seem  to  indicate  that  they  are  tautomeric 
forms  as  above,  and  that  the  geometric  isomer  of  the  sulphonic  acid 
compound  is  not  known. 

Thus  the  acceptance  of  the  Bloomstrand-Strecker-Erlenmeyer 
formula  for  the  diazonium  base  and  salts,  and  of  the  Hantzsch  modi- 
fication of  the  Kekule  formula  for  the  isomeric  diazotates  and  the  acid 
diazo  hydroxide,  together  with  the  tautomeric  transformations  which 
occur,  makes  possible  the  explanation  of  all  the  facts  which  we  have 
considered  in  the  preceding  discussion.  These  may  be  stated  again 
briefly  for  the  sake  of  emphasis  and  review,  (i)  The  reaction  of 
diazotization,  (2)  the  diazonium  base  and  salts,  (3)  the  diazotates  and 
acid  diazo  hydroxide,  (4)  the  isomerism  of  the  diazotates,  (5)  the 
diazonium  sulphites  and  diazo  sulphonic  acids,  (6)  the  relationship  of 
diazo  compounds  to  nitroso  amines,  (7)  to  hydrazines,  (8)  the  coupling 
with  amino  and  hydroxy  compounds  to  form  amino  azo  and  hydroxy 
azo  compounds,  (9)  the  reactions  of  decomposition.  Most  of  these 
last  reactions  we  have  not  considered,  but  will  do  so  presently  and  we 
shall  find  that  they  all  may  be  likewise  satisfactorily  explained.  The 
tautomeric  constitution  of  the  diazo  compounds,  therefore,  meets  every 
test  and*is  generally  accepted. 

Diazo  Esters. — Before  taking  up  the  reactions  of  decomposition  of 
diazo  compounds  there  is  one  other  class  of  derivatives  which  should 
be  mentioned.  As  an  acid  compound  benzene  diazo  hydroxide  yields 
esters,  not  by  the  direct  action  of  alcohols,  but  by  the  action  of  alkyl 
halides  upon  silver  diazotate.  These  esters  are  stable  compounds  like 


DIAZO   COMPOUNDS 


595 


the  iso-diazotate  and  are  able  to  be  isolated  and  studied.  The  methyl 
ester  of  nitro  diazo  benzene  will  be  given  as  an  illustration. 

N=N— OCH3 
C«H/ 

XN02(p) 

para-Nitro  benzene 
diazo  methyl  ester 

This  compound  crystallizes  in  needles  which  are  colorless  and  which 
melt  at  83°.  It  is  insoluble  in  water,  but  soluble  in  alcohol  or  ether. 
Its  reactions  prove  it  to  be  a  true  diazo  compound.  It  is  formed  by  the 
action  of  methyl  iodide  upon  either  the  silver  nitro  diazotate  or  iso- 
diazotate. 

Reactions  of  Di-azo  Compounds 

The  reactions  of  diazo  compounds  are  of  two  types,  (i)  Reactions 
by  which  the  nitrogen  group  is  left  intact.  In  these  the  nitrogen  group 
may  be  unchanged  in  character,  the  products  being  derivatives  of  diazo 
compounds,  e.g.,  diazonium  salts,  diazotates,  diazonium  sulphites,  diazo 
sulphonic  acids;  or  the  nitrogen  group  may  be  changed  in  character 
yielding  other  classes  of  compounds,  e.g.,  rearrangement  to  isomeric 
nitroso  amines,  reduction  to  hydrazines,  or  coupling  to  form  azo  amino, 
amino  azo  or  hydroxy  azo  compounds.  All  of  the  reactions  of  this  type 
have  been  fully  considered  in  the  discussion  of  the  constitution  of  diazo 
compounds,  and  in  the  previous  study  of  azo  compounds.  (2)  Reac- 
tions of  decomposition  in  which  the  diazo  nitrogen  group  is  either 
partly  or  wholly  replaced.  The  reactions  of  this  second  type  we  shall 
now  consider.  We  shall  use  benzene  diazonium  chloride  as  the  example, 
but  it  should  be  emphasized  that  the  reactions  are  typical  of  any  diazo 
compound.  Detailed  directions  or  the  particular  conditions  under 
which  a  specific  reaction  takes  place  will  not  be  given,  but  may  be  found 
in  larger  texts  or  laboratory  guides. 

Reduction  to  Hydrocarbons. — By  reducing  agents  diazo  compounds 
yield  the  corresponding  hydrocarbon,  the  diazo  group  being  replaced  by 
hydrogen.  We  have  already  stated  (p.  587)  that  by  reduction  diazo 
compounds  yield  hydrazines  in  which  case  the  diazo  group  remains 
intact  though  changed  in  character.  This  is  evidently  a  further  step 
in  the  complete  reduction  which  finally  results  in  the  hydrazine  being 
split  into  aniline  and  ammonia  for  the  hydrazine  may  also  be  trans- 


OEGANIC  CHEMISTRY 

formed  back  to  the  diazo  compound  by  oxidation  with  copper  sulphate 
or  ferric  chloride.  The  following  reactions  will  illustrate. 

(C2H5— OH) 
C6H5— N— Cl  +  H2 C6H6  +  HC1  +  N2 

HI  (SnCl2)        Benzene 

N 

Benzene  diazonium 
chloride 

+  2H2(Zn  +  CHaCOOH)  C6H5— NH 

C6H5— N— (Cl  " "  HC1+  |         +H2 

HI  +  0(CuS04)  NH2 

•j^r  Phenyl  hydrazine 

>     C6H5— NH2  +  NH3 

Aniline 

The  reduction  of  diazo  compounds  to  the  hydrocarbon  may  be  ac- 
complished by  means  of  stannous  chloride,  sodium  stannite  or  under 
certain  conditions  alcohols  act  as  a  reducing  agent  being  themselves 
thereby  oxidized  to  aldehydes. 

Hydrocarbons  of  another  class  than  the  one  corresponding  to  the 
diazo  compound  may  be  obtained  by  the  reaction  of  diazo  compounds 
with  a  hydrocarbon  in  the  presence  of  aluminium  chloride  (Friedel- 
Craft  reaction).  In  this  case  the  diazo  group  is  replaced  by  a  hydro- 
carbon radical. 

C6H5— N—  (Cl  +  H)— C6H5(+A1C13)  >  C6H5— C6H5  +  N2  +  HC1 

1 1 1  Phenyl  benzene 

,  Di-phenyl 

N 

Benzene  diazonium 


Oxidation. — When  oxidized  in  alkaline  solution  diazo  compounds 
are  converted  into  a  number  of  different  products,  in  some  cases  with 
the  loss  of  nitrogen  and  in  some  without.  In  alkaline  permanganate 
or  ferricyanide  solutions  benzene  diazonium  salts  yield  a  mixture  as 
follows : 

C6H5— N — Cl          by  alkaline  oxidation        > 

III 
N 

Benzene  diazonium  chloride 


DIAZO   COMPOUNDS  597 

C6H5— C6H5  Di-phenyl 

C6H5— N  =  N— C6H5  Azo  benzene 

C6H5— NH(NO2)  Phenyl  nitro  amine 

C6H5 — NO  Nitroso  benzene 

C6H5— NO2  Nitro  benzene 

As  the  oxidation  occurs  in  alkaline  solution  the  diazonium  salt  is  first 
converted  into  the  diazo  hydroxide  or  the  diazotate  and  this  is  then 
oxidized. 

Reaction  with  Water  Yields  Phenols. — With  water  at  ordinary  or 
at  raised  temperatures  diazonium  salts  readily  decompose,  the  nitrogen 
is  set  free  and  the  hydroxyl  compound  of  the  corresponding  hydrocarbon 
is  formed,  i.e.,  the  diazo  group  is  entirely  replaced  by  the  hydroxyl 
group.  Benzene  diazonium  chloride  thus  yields  hydroxy  benzene  or 
phenol. 


C6H5-|-N— (Cl  +  H)— OH     >.    C6H5— OH  +  HC1      +      N2 

Hydroxy  Nitrogen 

benzene 
i    TO-  Phenol  mol.  wt.  28 

Benzene  diazonium 
chloride 

mol.  wt.  140.4 

We  have  referred  to  this  reaction  as  being  the  second  step  in  the  action 
of  nitrous  acid  on  primary  amines  as  it  takes  place  in  the  aliphatic 
series  (p.  60).  This  explains  why,  in  most  cases,  it  is  necessary  to 
keep  the  temperature  low,  usually  at  about  o°,  during  diazotization 
for,  if  the  temperature  rises,  the  reaction  just  given  takes  place,  which, 
with  the  reaction  of  diazotization,  makes  the  whole  double  reaction 
exactly  the  same  as  in  the  case  of  aliphatic  amines.  The  nitrogen  set 
free  is  the  entire  amount  present  in  the  diazo  compound,  and  by  con- 
ducting the  operation  so  as  to  measure  the  evolved  nitrogen  gas,  the 
reaction  may  be  used  for  a  quantitative  determination  of  the  amount 
or  purity  of  the  diazo  compound,  28  parts  by  weight  of  nitrogen  (i  mol.) 
being  evolved  from  140.4  parts  by  weight  of  benzene  diazonium  chloride. 
Alcohols  Yield  Ethers. — With  alkalies  a  similar  reaction  does  not 
occur,  the  more  stable  diazotates  being  formed  (p.  591).  When 
heated  with  alcohols,  however,  the  diazo  compounds  act  in  an  exactly 
analogous  way  to  that  with  water.  In  this  case  if  an  aliphatic  alcohol 


598  ORGANIC  CHEMISTRY 

is  used  the  alkyl  oxy  group  replaces  the  diazo  nitrogen  group  and  an 
ether  results. 

C6H5  -i-N—  (Cl  +  H)—  OC2H5    -  >     C6H5—  O—  C,H6  +  N2  +  HC1 

j    IN  Phenyl  ethyl 

ether 

IN  ,; 

Benzene  diazonium 
chloride 

Under  certain  conditions  aromatic  ring  hydroxy  compounds  yield 
analogous  products  though  the  usual  reaction  is  the  one  already 
given  (p.  569)  by  which  hydroxy  azo  compounds  are  formed. 

Sulphur  Compounds.  —  The  two  preceding  reactions  with  water  and 
with  alcohol  may  be  carried  out  also  with  the  analogous  sulphur  com- 
pounds, viz.,  hydrogen  sulphide,  H  —  SH,  and  thio  -alcohols  or  mercap- 
tans,  e.g.,  C2Hs  —  SH.  The  product  in  the  first  case  is  a  thio-phenol, 
C6H6—  SH,  and  in  the  second  phenyl  ethyl  thio-ether,  C6H5—  S—  C2H5. 

Halogen  Acids  Yield  Aromatic  Halides.  —  When  a  water  solution 
of  a  diazonium  salt  is  heated  with  a  halogen  acid  the  halogen  substitu- 
tion product  of  the  corresponding  hydrocarbon  is  obtained,  the  diazo 
group  being  replaced  by  the  halogen. 

+  H)—  Br    —  >     C6H5—  Br  +  H2SO4  +  N2 

Brom  benzene 


Benzene  diazonium 
acid  sulphate 

Sandmeyer  Reaction.  —  It  was  found  that  in  the  presence  of  the 
cuprous  salt  of  the  halogen  acid,  CuCl  or  CuBr,  the  decomposition 
takes  place  more  easily,  a  double  copper  compound  being  probably 
formed  as  an  intermediate  step. 

C6H5—  N—  Cl  +  2CuCl(+  HC1)     --  >    C6H5—  N—  N—  Cl 

III  I       I 

N  CICu  CuCl 

Benzene  diazonium  Double  copper  compound 

chloride 

C6H5—  N—  N—  Cl    --  >     C6H5—  Cl  +  2CuCl  +  N2 

Chlor  benzene 

CICu  CuCl 

Copper  compound 


DIAZO   COMPOUNDS 


599 


This  is  known  as  the  Sandmeyer  reaction  and  it  is  usually  carried  out  at 
the  same  time  as  the  diazotization  so  that  by  starting  with  the  primary 
amine  the  halogen  product  is  obtained. 

'  Gattermann  Reaction. — The  reaction  was  further  modified  by  Gat- 
termann who  found  that  finely  divided  metallic  copper  could  be  used 
with  even  greater  advantage.  The  Sandmeyer  and  Gattermann  reac- 
tions are  not  applicable,  however,  for  the  formation  of  the  iodine  prod- 
ucts. To  form  these  the  diazonium  salt,  usually  the  acid  sulphate,  is 
heated  with  a  solution  of  potassium  iodide. 

C6H6-j-N—  (SO4H  +  K)— I  — >  C6H5— I  +KHSO4  +  N2 

lodobenzene 

I  N 

Benzene  diazonium 
acid  sulphate 

Cyanides  Yield  Nitriles. — Sandmeyer  also  applied  the  principle  of 
his  reaction  to  the  preparation  of  cyanide  substitution  products,  i.e., 
replacement  of  the  diazo  group  with  cyanogen  radical.  The  reaction 
is  brought  about  by  warming  a  diazonium  salt  solution  with  a  solution 
of  cuprous  cyanide  in  potassium  cyanide. 

C6H5-|-N— (Cl  +  CuCN.(K)CN    >     C6H5— CN  +  KC1  +  N2 

j    Ml  Phenyl  cyanide 

Benzoic  nitrile 

I  N 

Benzene  diazonium 
chloride 

Aromatic  Acids. — As  the  cyanides  are  acid  nitriles,  yielding  the 
acids  on  hydrolysis,  the  above  reaction  gives  us  a  means  of  passing 
from  primary  amines  through  the  diazo  compound  to  the  acid  nitrile 
and  finally  to  the  corresponding  aromatic  acid. 

C6H5— -  NH2         >        C6H6— N2— Cl        — r-» 

Aniline  Benzene  diazonium 

(primary  chloride 

amine) 

C6H6— CN  — >        C6H5— COOH 

Phenyl  Benzoic  acid 

cyanide 

The  following  tabular  arrangement  of  all  of  the  diazo  reactions  will 
bring  the  whole  matter  in  review. 


600 


ORGANIC  CHEMISTRY 


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ORGANIC  CHEMISTRY 


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604  ORGANIC  CHEMISTRY 

Looking  at  these  reactions  as  a  whole  we  can  not  fail  to  recognize  how 
extremely  reactive  the  diazo  compounds  are,  and  what  varied  products 
result.  The  instability  which  we  find  here  as  in  other  organic  nitrogen 
compounds,  while  not  of  practical  application  in  explosives,  gives  to  the 
compounds  their  exceeding  ease  of  reaction.  As  they  are  themselves 
prepared  from  primary  amines  of  the  aromatic  series,  and  as  the  amines 
are  either  natural  products  obtained  from  coal  tar  or  are  easily  pre- 
pared from  the  hydrocarbons,  through  the  like  easily  prepared  nitro 
compounds,  the  chemist  has,  in  the  diazo  compounds,  a  practical  means 
of  obtaining  a  large  variety  of  products.  These  products  may  have  a 
direct  value  as  dyes,  as  in  the  case  of  many  of  the  different  groups  of 
azo  compounds,  or  they  may  be  steps  in  the  preparation  of  other 
compounds,  as  is  true  of  most  of  the  decomposition  products  obtained 
by  replacing  the  diazo  group  with  hydrogen,  hydroxyl,  a  halogen,  cyano- 
gen, etc.  As  the  formation  of  diazo  compounds  takes  place  with  any 
primary  amine,  whether  a  simple  compound  or  a  complex  substitution 
product,  and  whether  of  benzene  or  its  homologues,  or  of  the  other 
series  of  hydrocarbons,  the  last  reactions  just  referred  to  are  used  as  a 
means  of  obtaining  practically  any  derivative  of  the  classes  given. 
Thus  both  industrially  and  theoretically  the  diazo  compounds  are  of 
great  practical  use,  not  in  themselves  as  isolated  compounds,  but  as 
steps  in  the  preparation  of  other  products. 

RESUMfi  OF  NITROGEN  DERIVATIVES 

In  the  last  four  main  groups  of  benzene  derivatives,  viz.,  the  nitric 
and  nitrous  acid  derivatives,  the  ammonia  derivatives  or  amines,  the 
intermediate  reduction  products  of  nitro  compounds,  and  the  diazo 
compounds,  we  have  to  do  with  organic  compounds  containing  nitrogen. 
These  four  groups  do  not  include  all  of  the  organic  nitrogen  compounds 
of  the  aromatic  series,  as  the  large  and  important  group  of  basic  nitrogen 
compounds  including  the  alkaloids  will  be  studied  later.  Even  with 
this  exception  the  four  groups  considered  show  us  how  important  the 
aromatic  nitrogen  compounds  are.  The  presence  of  nitrogen  in  the 
molecule  endows  the  compounds  with  many  characteristic  properties 
such  as  instability,  resulting  in  extreme  reactivity  and  often  connected 
with  explosive  character.  The  compounds  also  often  exhibit  the 
phenomena  of  isomerism  both  structural  and  stereo-,  and  of  tautomerism. 


RESUME    OF   NITROGEN  DERIVATIVES  605 

Practical  application  of  the  explosive  character  of  nitrogen  compounds 
is  found  in  the  case  of  the  nitro  compounds  such  as  tri-nitro  toluene 
and  nitro  phenols  such  as  picric  acid  (p.  630)  which  are  analogous  as 
nitro  compounds  to  similar  explosives  of  the  aliphatic  series,  e.g., 
nitro  glycerol  and  nitro  cellulose.  The  chemical  reactivity  of  the 
nitrogen  compounds  as  shown  in  their  ability  to  yield  a  large  variety 
of  products  is  found  in  the  groups  of  amines,  the  intermediate  reduction 
products  of  nitro  compounds  and  above  all  in  the  diazo  compounds. 
All  of  these  groups  are  associated  in  their  relation  to  the  numerous 
important  products  used  as  dyes,  in  particular  those  of  the  azo  and  ben- 
zidine  classes,  while  the  amines  themselves  are  related  to  other  like 
important  dyes  such  as  the  tri-phenyl  methane  and  indigo  classes 
Thus  as  a  large  class  the  aromatic  nitrogen  compounds  are  almost 
without  a  parallel  as  to  their  importance  both  from  an  industrial  or 
economic  and  from  a  theoretical  viewpoint. 


VII.  HYDROXYL  DERIVATIVES 
A.  PHENOLS 

(Hydroxyl  in  the  ring) 

We  come  now  to  the  hydroxyl  substitution  products  of  the  benzene 
hydrocarbons.  These  derivatives  are  of  two  classes:  A,  phenols, 
in  which  the  hydroxyl  group  is  substituted  in  the  ring  part  of  the 
compound.  B,  alcohols,  in  which  the  hydroxyl  group  is  substituted  in 
the  side  chain  of  benzene  homologues.  Benzene  having  no  side  chain 
yields  only  the  first  class  of  derivatives.  Toluene,  however,  and  all 
the  other  homologues  of  benzene  yield  both  classes  as  follows: 

CH3  CH3  CH2OH 

I  I  I 

c  c  c 

—  OH 


HcL  JcH  HcL  J 


H  H  H 

Toluene  Phenol  Alcohol 

o-Cresol  Benzyl  alcohol 

i  -Methyl  2-hydroxy 
benzene 

Phenols.  —  The  ring  hydroxyl  compounds  take  the  class  name  of 
phenols  from  the  simplest  member,  hydroxy  benzene  or  phenol.  These 
are  true  aromatic  compounds  and  in  methods  of  formation,  reactions 
and  properties  are  distinctly  different  from  aliphatic  hydroxyl  com- 
pounds or  alcohols.  Their  outstanding  distinction  is  their  marked 
acid  character,  the  alcohols  being  neutral  (p.  103).  This  is  attributed 
to  the  influence  of  the  phenyl  radical  (C6H5  —  ).  The  same  influence  is 
present  in  the  amino  derivatives,  for  the  ring  amines,  C6HB  —  NH2, 

/CH3 
aniline,  C6H4<T          >  toluidine,  etc.,  are  less  basic,  i.e.,  more  acid,  than 

aliphatic  amines,  e.g.,  CH3  —  NH2,  methyl  amine,  and  also  than  C6H5  — 
NH(CH3),  mono-methyl  aniline,  or  C6H5—  N(CH3)2,di-methyl  aniline. 

606 


PHENOLS    AND    THEIR   DERIVATIVES 


607 


Alcohols. — The  side  chain  hydroxyl  compounds  take  the  class 
name  of  alcohols  for  they  are  true  aromatic  alcohols  in  formation, 
reaction  and  properties.  They  are  neutral,  not  acid,  and  are  formed 
by  methods  analogous  to  those  by  which  the  aliphatic  alcohols  are 
prepared.  They  may  be  looked  upon  as  benzene  derivatives  of  ali- 
phatic alcohols,  e.g.,  C6H5 — CH2OH,  benzyl  alcohol  or  phenyl  methyl 
alcohol. 

The  acidic  influence  of  the  benzene  ring  or  phenyl  radical  may  be 
illustrated  by  a  comparison  of  the  two  series  of  compounds  given 
below. 

AROMATIC  CHARACTER  ALIPHATIC  CHARACTER 

ring  substitution  chain  substitution 

(more  acid;  less  basic)  (more  basic;  less  acid) 

Phenols  Alcohols 

Phenol,  C6H6— OH  CH3— OH,  Methyl  alcohol 


C6H6— CH2— OH,     Benzyl  alcohol 


Cresol, 

OH 

Amines 

C6H5—  NH2 
/CH3 
C6H4<^ 

XNH2 

Di-phenyl  amine,    C6H5—  NH—  C6H6 
Tri-phenyl  amine,  (C6H5)  sN 


Aniline, 
Toluidine, 


Amines 
CHs— NH2,  Methyl  amine 

C?H5— CH2— NH2,    Benzyl  amine 


C6H5— NH— CH3,  Mono-methyl  aniline 
C6H5— N(CH3)2,      Di-methyl  aniline 
(CH  3)  3N,  Tri-methyl  amine 

If  we  examine  the  complete  benzene  ring  formulas  for  the  phenols  we 
see  that  the  carbon-hydroxyl  group  is  of  the  same  nature  as  in  tertiary 
alcohols. 

OH 


CH3 

H3C— C— OH 

I 
CH3 

Tertiary  butyl  alcohol 


HC 
HC 


C 

O 


CH 
CH 


C 
H 

Phenol 


608  ORGANIC  CHEMISTRY 

In  both  cases  the  carbon  atom  linked  to  the  hydrox^l  has  the  three 
other  valencies  satisfied  by  carbon  groups.  In  the  tertiary  alcohols 
three  separate  carbon  groups  satisfy  the  three  valencies  while  in  the 
phenol  only  two  carbon  groups  satisfy  the  three  valencies,  one  of  them 
being  doubly  linked.  The  phenols  thus  are  not  even  in  this  respect 
exactly  like  the  alcohols,  and  though  they  do  resemble  the  tertiary 
alcohols  in  not  yielding  either  aldehydes  or  ketones  on  oxidation,  due 
to  the  fact  that  no  hydrogen  atom  is  linked  to  the  hydroxyl  carbon 
atom,  yet  the  fact  that  they  are  distinctly  different  from  the  alcohols 
should  always  be  kept  in  mind. 

Mono-  and  Poly -phenols. — As  with  the  other  ring  substitution  prod- 
ucts of  benzene  and  its  homologues  we  have  not  only  mono-,  but  also 
di-,  tri-  and  other  poly-substitution  products,  so  also  we  have  poly- 
phenols  in  which  more  than  one  hydrogen  atom  of  the  ring  is  substituted 
by  the  hydroxyl  group.  In  these  poly  phenols  the  conditions  of  posi- 
tion isomerism  are  present  so  that  ortho,  meta  and  para;  vicinal, 
symmetrical  and  unsymmetrical  isomers  are  known. 

Syntheses 

.  From  Sulphonic  Acids. — As  previously  stated,  the  methods  of 
formation  of  phenols  are  wholly  different  from  those  of  alcohols,  and, 
together  with  their  reactions,  prove  the  constitution  to  be  as  we  have 
given  it,  viz.,  Ring — OH.  The  synthesis  which  is  most  generally  used 
industrially  is  that  from  sulphonic  acids,  (p.  520).  When  a  salt  of 
benzene  sulphonic  acid  is  fused  with  potassium  or  sodium  hydroxide, 
phenol  is  formed  together  with  a  sulphite  salt  of  the  metal,  according  to 
the  following  reaction: 

C6H5—  (SO2OK+K)— OH        4        C6H5— OH+K2SO3 

Benzene  Phenol 

sulphonic  acid  Hydroxy 

(salt)  benzene 

The  phenol  is  present  in  the  fusion  product  as  the  potassium  salt  formed 
by  neutralization  of  the  acid  phenol  with  the  excess  of  alkali.  On 
acidifying  the  phenol  separates  and  at  the  same  time  sulphur  dioxide 
is  evolved  proving  that  a  salt  of  sulphurous  acid  is  present.  The  relation 
of  this  reaction  to  the  sulphonic  acids  and  to  sulphurous  acid  has  been 
discussed  in  connection  with  the  sulphonic  acids  (p.  520). 

From  Diazo  Compounds. — Another  synthesis  of  phenols  that  is  often 
used  in  the  laboratory,  especially  if  the  desired  sulphonic  acid  is  not 


PHENOLS   AND   THEIR  DERIVATIVES  609 

known  or  is  unavailable,  is  the  one  from  diazo  compounds  which  has 
already  been  given  in  connection  with  the  reactions  of  these  com- 
pounds (p.  597).  When  decomposed  by  water  diazonium  salts  have 
the  diazo  group  replaced  by  hydroxyl. 


C6H5- 


-N—  (Cl+H)— OH    >    C6H5— OH+N2+HC1 


Phenol 


.    N 
Benzene 
diazonium 

salt 

This  synthesis  gives  a  method  of  preparing  phenols  from  amino  deriva- 
tives by  first  diazotizing  these  and  then  decomposing  the  diazo  com- 
pound as  above.  Also  nitro  derivatives  may  be  reduced  to  amines 
and  then  converted  into  phenols.  Thus  from  either  of  these  classes  of 
compounds  by  means  of  the  diazo  reactions  we  may  obtain  the  corre- 
sponding phenol  with  the  hydroxyl  group  in  the  position  of  the  original 
nitro  or  amino  group.  Such  a  result  is  often  desired  in  synthetic  work 
and  the  diazo  synthesis  of  phenols  is  of  great  importance. 

From   Hydrocarbons.  —  In    the   presence   of   aluminium    chloride 
(Friedel-Craft  reagent)  benzene  may  be  oxidized  to  phenol. 


C6H5—  H    +    O(+A1C1,)        --  >        C6H5—  OH 

Benzene  Phenol 

It  will  be  recalled  that  aliphatic  hydrocarbons  containing  a  tertiary 
carbon  group,  CH3—  CH(CH3)—  CH3, 

are  easily  oxidized  to  tertiary  alcohols  (p.  239).  This  emphasizes  the 
tertiary  alcohol  similarity  of  the  phenols  before  referred  to.  In  the  case 
of  di-phenols  it  is  a.  striking  fact  that  they  may  be  prepared  by  oxidizing 
a  mono-phenol  by  means  of  hydrogen  dioxide. 

/OH  /OH 

C6H4<  +     H202       -*     C6H4<  +    2H20 

'    \H  \OH 

Mono-hydroxy  Di-hydroxy 

benzene  benzene 

Reactions  of  this  kind  do  not  occur  in  the  aliphatic  series. 

From  ilydroxy  Acids.  —  Carboxylic  acids  when  heated  with  soda 
lime  lose  carbon  dioxide  and  yield  the  hydrocarbon.  By  a  similar 
reaction  hydroxy  acids,  either  aliphatic  or  aromatic,  which  contain  a 

39 


6 10  ORGANIC  CHEMISTRY 

hydroxyl  group  as  well  as  a  carboxy],  yield  the  hydroxyl  derivative 
of  the  hydrocarbon. 

C6H5— COOH        >        C6H6  +  CO2 

Benzole  acid  Benzene 

/COOH 
C6H21  >         C6H3  ^  (OH)  3  +  C02 


>(OH)3  Tri-hydroxy 

Tri-hydroxy  .         benzene 

benzole  acid 

The  reaction  is  not  practical  for  the  preparation  of  phenol  itself,  but  is 
used  in  the  case  of  the  tri-hydroxy  benzene,  pyro-gallol  or  pyro-gallic 
acid. which  is  obtained  by  heating  gallic  acid,  which  is  tri-hydroxy  ben- 
zoic  acid,  as  above. 

From  Aryl  Halides. — We  have  said  that  phenols  are  not  prepared 
by  the  same  general  reactions  as  are  used  in  preparing  the  aliphatic 
hydroxyl  compounds.  This  is  true  in  general  though  we  shall  give 
an  interesting  exception.  Aliphatic  alcohols  are  most  easily  synthe- 
sized by  treating  the  alkyl  halides  with  silver  hydroxide,  or  with 
potassium  hydroxide. 

CH3— (I  +  Ag)— OH        >        CH3— OH  -f  Agl 

Methyl  Methyl  alcohol 

iodide 

With  the  simple  aryl  halides  such  as  the  mono-chlor  derivatives  of 
benzene  or  its  homologues  this  reaction  does  not  take  place.  If,  how- 
ever, a  benzene  halide  has  also  substituted  in  the  ring  two  nitro,  sul- 
phonic  acid  or  carboxyl  groups,  in  the  ortho  and  para  positions  to  the 
halogen,  then  treatment  of  the  halide  with  potassium  hydroxide  results 
in  replacing  the  halogen  with  hydroxyl  and  the  corresponding  substi- 
tuted phenol  will  be  obtained. 

From  Natural  Sources. — In  addition  to  their  synthetic  preparation 
many  of  the  phenols  are  obtained  by  the  distillation  of  natural  sub- 
stances, e.g.,  coal  (coal  tar),  wood,  resins,  etc.  Phenol  is  obtained 
from  coal  tar,  while  the  hydroxy  toluenes  or  cresols  are  obtained  from 
both  wood  tar  and  coal  tar  as  indicated  by  the  term  creosote  for  the 
crude  distillation  products  of  wood. 

Properties  and  Reactions 

The  mono-phenols  are  liquids  or  low  melting-point  crystalline  solids, 
while  the  poly-phenols  are  crystalline  solids  only.  The  mono-phenols 


PHENOLS   AND   THEIR  DERIVATIVES  6ll 

are  soluble  in  alcohol  or  ether  but  only  slightly  so  in  water.  As  the 
number  of  hydroxyl  groups  increases,  the  solubility  in  water  also  in- 
creases, the  di-  and  tri-hydroxyl  derivatives  being  easily  soluble  in  water. 
Salts. — As  has  been  stated,  the  acid  nature  of  the  phenols  is  a  dis- 
tinctive character.  This  is  especially  true  of  the  lower  members, 
phenol,  the  simplest  member,  being  commonly  known  as  carbolic  acid. 
In  the  case  of  certain  substituted  phenols  the  acid  character  is  even 
more  marked,  e.g.,  picric  acid,  which  is  tri-nitro  phenol.  As  acids 
the  phenols  readily  form  salts  termed  phe/iolates. 

C6H5— OH    +    K— OH  -»        C6H5— OK    +    H2O 

Phenol  Potassium 

phenolate 

While  alcohols  also  form  alcoholates  (p.  79),  the  phenolates  are  more 
stable  and  more  definitely  salt-like  in  character  due  to  the  more  strongly 
acid  nature  of  the  phenyl  or  other  aryl  radical.  The  phenolates,  how- 
ever, are  decomposed  by  carbon  dioxide  and  react  alkaline  to  some 
indicators. 

Esters. — While  not  true  alcohols,  the  phenols  nevertheless  possess 
alcoholic  character  as  already  referred  to  in  speaking  of  their  similarity 
to  tertiary  alcohols.  This  is  shown  in  their  formation  of  both  esters 
and  ethers.  Esterification  is  as  a  rule  less  easy  than  with  alcohols. 
Phenolates  absorb  carbon  dioxide  directly  yielding  a  compound  that  is 
a  mixed  ester  and  salt  of  carbonic  acid. 

C6H5— ONa  +  CO2     >     C6H5— O— CO— ONa 

Sodium  phenolate  Sodium  phenyl  carbonate 

This  compound  will  be  referred  to  again  in  connection  with  the  synthesis 
of  salicylic  acid  (p.  717).  The  acid  ester  of  phenol  and  sulphuric  acid, 
phenyl  sulphuric  acid,  C6H5 — O — SO2OH,  is  a  constituent  of  animal 
urine.  The  esters  of  phenols  and  organic  acids  are  not  readily  formed 
by  the  direct  action  of  the  acids,  in  which  respect  the  phenols  again 
resemble  tertiary  alcohols.  They  may  be  prepared  from  phenols  by 
the  action  of  acid  chlorides,  acid  anhydrides  or  a  mixture  of  the  acid 
and  phosphorus  oxychloride. 

C6H8— 0— (H  +  Cl)— OC— CH3       ->    C6H6— 0— OC— CH3 

Phenol  Acetyl  Phenyl  acetate 

chloride 


6l2  ORGANIC  CHEMISTRY 

Ethers.  —  Ethers  of  the  phenols  may  be  formed  by  means  of  the 
Williamson  reaction  when  phenolates  are  treated  with  alkyl  halides. 

C6Hfi—  O(K  +  I)—  CH3    -  >     C6H5—  O—  CH3  +  KI 

Potassium  Phenyl  methyl  ether 

phenolate  Anisole 

C6H5—  O(K  +  I)—  C2H5  —  >  C6H5—  O—  C2H5  +  KI 

Phenyl  ethyl  ether 
Phenetole 

These  two  ethers,  known  as  anisole  and  phenetole,  are  well  known 
compounds. 

Reaction  with  PC15.  —  With  phosphorus  penta-chloride  the  phenols 
react  as  alcohols  yielding  the  aryl  halide. 

C6H5—  OH  +  PCU    -  >     C6H6—  Cl  +  POC13  +  HC1 

Phenol  Phenyl 

chloride 

With  Ammonia.  —  With  ammonia,  in  the  form  of  ammonia  zinc 
chloride,  ZnCl2—  4NH3,  phenols,  especially  the  poly-phenols,  yield 
amino  compounds  by  replacement  of  a  hydroxyl  with  an  amino  group. 

,OH  , 

C6H/        +ZnCl2.4NH3       ->     C6H/ 


Di-hydroxy  Amino  phenol 

benzene 

Reduction  and  Oxidation.  —  By  reduction  with  zinc,  phenols  yield 
hydrocarbons. 

C6H5—  OH  +  Zn       -3    C6H6 

Phenol  Benzene 

Oxidation  of  phenols  yields  a  variety  of  products.  Hydrogen  dioxide 
gives  a  di-hydroxyl  product  while  by  fusion  with  caustic  soda  both  di- 
and  tri-hydroxyl  products  are  obtained. 

/OH 
C6H5—  OH  +  H2O2     -  >     C6H/ 

Phenol  ^OTT 

Di-hydroxy  benzene 

/OH 
C6H5—  OH  +  O(NaOH  fusion)        —>     CeH 


Tri-hydroxy  benzene 


PHENOLS   AND   THEIR   DERIVATIVES  613 

The  phenols  of  the  benzene  homologues,  e.g.,hydroxy  toluenes  or  cresols, 
have  the  side  chain  group  oxidized  to  carboxyl  and  yield,  therefore,  a 
hydroxy  acid. 

COOH 


y 
C6H  +0       ->     C6H/ 

XOH  \)H 

Hydroxy  toluene  Hydroxy  benzole  acid 

Substitution  in  the  Ring.  —  With  nitric  and  sulphuric  acids  phenols 
yield  substitution  products  more  easily  than  do  the  hydrocarbons  them- 
selves. 

yOH  OH 

C6H/        +  HO)—  N02       -»    C6H/ 

X(H  XN02 

Phenol  Nitro  phenol 

Color  Reactions.  —  Many  of  the  derivatives  of  phenol  are  highly 
colored,  especially  the  nitroso  and  nitro  compounds.  The  formation 
of  these  compounds  under  qualitative  conditions  is  often  made  use  of  in 
testing  either  for  a  phenol  or  for  nitrous  or  nitric  acid  or  a  derivative. 
With  ferric  chloride,  FeCl3,  phenols  give  characteristic  colors,  blue, 
green,  red  or  violet.  Phenol  ethers  do  not  respond  to  these  tests. 

Liebermann's  Nitroso  Reaction.  —  When  phenol  in  sulphuric  acid, 
phenyl  sulphuric  acid,  is  treated  with  a  nitrite  or  with  a  nitroso  amine 
a  dark  green,  red  or  brown  color  is  obtained  which  changes  to  blue  or 
green  on  addition  of  an  alkali.  The  test  is  known  as  Liebermann's 
nitroso  reaction,  and  may  be  used  in  testing  for  a  phenol,  a  nitrite  or  a 
nitroso  amine. 

MONO-PHENOLS,  MONO-HYDROXY  BENZENES 
Phenol,  CeH6  —  OH,  Hydroxy  Benzene,  Carbolic  Acid 

The  simplest  ring  hydroxyl  derivative  of  the  benzene  hydrocarbons 
is  mono-hydroxy  benzene,  C6H5  —  OH.  It  is  known  as  phenol  and  gives 
its  name  to  the  entire  class  of  ring  hydroxy  compounds.  The  name 
phenol  is  derived  from  the  Greek  word  (paiveiv,  meaning  to  light, 
and  signifies  the  occurrence  of  the  substance  in  the  products  of 
illuminating  gas  manufacture  (p.  497)  .  The  prefix  phen  is  also  retained 
in  the  term  phenyl  for  the  benzene  radical,  (CeH5  —  ).  Phenol  is  a  com- 
mon pharmaceutical  product  and  is  known  in  pharmacy  and  medicine 
as  carbolic  acid  indicating  its  acid  properties.  This  name  also  signifies 


6 14  ORGANIC  CHEMISTRY 

its  occurrence  in  coal  tar,  being  a  contraction  of  carbon  oil  acid.  It  is 
one  of  the  five  most  important  products  of  coal  tar  distillation  in  which 
it  was  first  discovered  in  1834  by  Runge.  It  also  occurs  in  small 
amounts  in  wood  tar  and  in  the  distillation  products  of  bones.  It  is 
present  as  the  sulphuric  acid  ester,  phenyl  sulphuric  acid,  C6H6 — O — SO2- 
— OH,  in  animal  urine. 

Phenol  when  pure  is  a  colorless  crystalline  substance  with  a  charac- 
teristic odor;  m.p.  42.5°,  b.p.  181.5°.  The  presence  of  a  small  amount 
of  water  lowers  the  melting  point  to  about  16°,  through  the  formation 
of  a  crystalline  hydrate,  2C6HB — OH.H2O.  With  more  water  a  solu- 
tion of  water  in  phenol  results  which  remains  liquid.  Water  is  soluble 
in  phenol,  1:3,  while  phenol  is  soluble  in  water  at  ordinary  tempera- 
tures, i  :  16. 

Poison  and  Antiseptic. — It  is  miscible  in  all  proportions  with  alcohol 
or  ether.  Phenol  is  a  very  strong  poison  and  is  caustic  to  the  skin 
producing  bad  burns.  As  an  antidote  for  phenol  poisoning  lime  or 
chalk  is  used.  It  is  an  extremely  important  medicinal  substance 
because  of  its  antiseptic  and  disinfectant  properties,  both  the  hands 
and  instruments  of  surgeons  being  rendered  aseptic  by  washing  in  a 
dilute,  2  to  3  per  cent,  solution  which  is  the  strength  commonly  used  as 
an  aseptic  wash.  It  has  many  other  important  uses,  as  some  of  its 
derivatives,  which  we  shall  mention  later,  are  valuable  as  dyes,  explo- 
sives and  photographic  developers.  The  test  for  phenol  is  the  one  with 
ferric  chloride,  as  previously  given. 

Commercial  Preparation. — The  most  important  method  for  prepar- 
ing phenol  on  a  commercial  scale  is  the  potash  fusion  of  benzene  sul- 
phonate  (p.  520),  though  it  may  also  be  prepared  by  the  diazo  synthesis 
(p.  597).  Its  chief  natural  source  is  coal  tar,  from  which  it  is  obtained 
in  the  fractions  of  coal  tar  distillation,  boiling  below  210°,  i.e.,  in  the 
light  and  middle  oils  (p.  497).  The  process  of  isolating  it  has  been 
described  (p.  498),  the  purest  product  being  in  the  form  of  the  hydrate, 
m.p.  1 6°.  The  yield  from  coal  tar  is  0.4  to  0.5  per  cent,  it  being  one  of 
the  five  most  important  coal  tar  distillation  products. 

/CH,, 

Cresols       C6H4<f  Mono-hydroxy  Toluenes 

XOH  , 

Mono-hydroxy  toluene,  being  a  di-substitution  product  of  benzene, 
i.e.,  methyl  hydroxy  benzene,  exists  in  isomeric  forms  as  ortho,  meta  and 


PHENOLS    AND    THEIR   DERIVATIVES 


615 


para  compounds.  They  are  known  as  cresols  and  are  found  in  wood 
tar,  and  in  coal  tar  in  the  same  fractions  of  the  distillate  as  phenol.  In 
the  higher  fractions  termed  creosote  oils  they  are  also  present,  but  are 
not  usually  separated  commercially.  The  yield  of  cresols  from  coal 
tar  is  about  2  to  3  per  cent. 

Tri-cresol. — The  product  as  obtained  from  coal  tar  is  a  mixture  of 
all  three  isomers  and  is  known  as  tri-cresol.  The  properties  of  the 
cresols  are  in  general  like  those  of  phenol.  They  also  are  valuable 
antiseptics  being  largely  used  as  disinfectants. 


C6H4 


'CH3  (i) 
\OH   (2) 


C6H4 


'CH3  (i) 


orlho-Cresol 
i -Methyl  2-hydroxy  benzene 

m.p.  31° 
b.p.  188° 


meta-Cresol 

i -Methyl  3-hydroxy 

benzene 

m.p.  4° 
b.p.  201° 


/CH3  (i) 
CeH/ 

\OH    (4) 

para-Cresol 
i -Methyl  4-hydroxy 
benzene 

m.p.  36° 
b.p.  198° 


The  synthesis  of  the  cresols  may  be  accomplished  by  the  general 
methods  for  synthesizing  phenols,  the  meta-cresol  being  also  synthesized 
from  thymol  (p .  6 1 6) .  The  ortho-  and  para-cresols  occur  as  the  sulphuric 
acid  esters  in  human  urine,  and  in  larger  amounts  in  the  urine  of  horses. 
para-Cresol  is  a  product  of  the  putrefaction  of  proteins. 


Carvacrol  and  Thymol  C6H3 


'CH3 

OH  Mono-hydroxy  Cymene 

-CH— CH3 


CH3 

Only  two  of  the  higher  homologous  mono-hydroxy  phenols  will  be 
mentioned.  These  are  the  two  isomeric  mono-hydroxy  cymenes, 
cymene  being  i -methyl  4-iso-propyl  benzene.  They  are  as  follows: 

CH3  CH3 


OH 


H3C— CH— CH3 

Thymol 

i -Methyl  4-iso-propyl 
3-hydroxy  benzene 


H3C— CH— CH3 

Carvacrol 

i -Methyl  4-iso-propyl 
2-hydroxy  benzene 


6l6  ORGANIC  CHEMISTRY 

The  proofs  for  the  above  constitutions  are  as  follows:  (i)  Thymol 
yields  cymene,  I  -methyl  4 -iso-propyl  benzene,  by  loss  of  the  hydroxyl 
oxygen  by  means  of  phosphorus  penta-sulphide.  (2)  Carvacrol  may 
be  synthesized  from  potassium  cymene  sulphonate  by  fusion  with 
potassium  hydroxide.  Therefore  both  must  be  mono-hydroxy  cymenes. 
(3)  Thymol  by  means  of  phosphorus  pentoxide  splits  off  the  iso-propyl 
radical  yielding  meta-cresol  and  propylene.  (4)  Carvacrol  by  the 
same  reaction  yields  ortho-cresol.  Therefore  in  thymol  the  hydroxy 
group  is  meta  to  the  methyl  group  while  in  carvacrol  it  is  ortho.  The 
following  relationships  are  thus  established. 

/CH3  (i)  7CH3  (i)  /CH3  (i) 

^OH  (3)       -- *     C6H/  < C6H3f  OH  (2) 

\CH— CH3(4)  \CH— CH3(4)  \CH— CH3(4) 

CH3                                            CH3  CH3 

Thymol                                                Cymene  Carvacrol 

i  i -Methyl  4-iso-propyl  I 

4-                                                 benzene  + 

/CH3(i)  /CH,(i) 

C.H/  CtHX 

XOH  (3)  XOH  (2) 

meta-Cresol  ortho-Cresol 

Terpenes  and  Camphor. — The  importance  of  these  two  phenols  is 
in  their  natural  occurrence  as  ethers  in  ethereal  oils  of  many  plants,  e.g., 
oil  of  thyme  and  oil  of  caraway,  and  especially  in  their  relationship  to 
the  terpenes  and  camphor,  as  will  be  shown  later  (p.  826,  834). 

Phenols  derived  from  benzene  homologues  containing  an  unsatu- 
rated  side  chain  will  be  mentioned  later  in  discussing  ether  derivatives  of 
phenols  (p.  622). 


POLY-PHENOLS,  POLY-HYDROXY  BENZENES 

The  poly-phenols  or  poly-hydroxy  benzenes  are  obtained  from  the 
dry  distillation  products  of  wood.  The  methods  of  synthesis  are  in 
general  those  for  the  mono-phenols  though  the  diazo  reaction  does  not 
usually  work  well  with  amino  phenols.  Also  some  of  the  methods  of 
preparation  used  for  poly-phenols  do  not  apply  to  the  mono-phenols. 
In  general  properties  they  resemble  the  mono-compounds,  but  they 
are  usually  more  easily  soluble  in  water,  react  more  readily  and  are 
characterized  by  their  strong  reducing  properties. 


PHENOLS   AND    THEIR   DERIVATIVES  617 

/OH 
Di-hydroxy  Benzenes,  CeH^ 

^OH 

All  three  of  the  isomeric  di-hydroxy  benzenes  are  known  and  their 
respective  constitutions  have  been  established  through  their  relation- 
ships to  the  three  xylenes  and  the  three  phthalic  acids  (p.  687). 

Pyro-catechinol,  1-2  -Di-hydroxy  Benzene.  —  The  ortho-di-hydroxy 
benzene  is  known  as  pyro-catechinol  or  pyro-catechin.  The  first 
name  is  preferable  as  the  termination  ol  indicates  its  phenol  character. 
Its  name  also  indicates  its  relation  to  a  resin  known  as  catechu,  obtained 
from  an  acacia  tree.  On  distillation  it  yields  the  phenol,  the  prefix 
pyro  meaning  heat.  It  is  also  present  in  the  dry  distillation  products 
of  wood,  coal  or  bituminous  shale.  Various  plant  materials  such  as 
resins  and  the  leaves  of  ampelopsis  yield  it  by  alkali  fusion.  It  is  also 
associated  with  phenol  as  a  sulphuric  acid  ester  in  the  urine  of  horses. 

The  best  methods  of  synthesis  are  the  potash  fusion  of  phenol 
ortho-sulphonic  acid  and  from  ortho-chlor  phenol  with  alkali. 

OH  OH 

C6H4<  -}-  KOH(fusion)        —  > 


SO2OK(o)  OH(o) 

Phenol  ortho-  Pyro-catechinol 

sulphonic  acid,  salt 


, 
C6H  +KOH  ->         C«H/ 

XC1(2)  XOH(2) 

ortho-Chlor  phenol  Pyro-catechinol 

Guaiacol.  —  Another  common  method  of  preparing  this  phenol  is 
from  one  of  its  derivatives  known  as  guaiacol,  a  naturally  occurring  sub- 
stance (p.  621).  It  is  the  methyl  ether  of  the  di-phenol  which  it 
yields  on  heating  with  water  and  aluminium  chloride. 


/  / 

C6H4<(  +  H—  OH(  +  A1C13)        ->     C6H/ 

X0-CH3(2)  X)H(2) 

Guaiacol  Pyro-catechinol 

Pyro-catechinol  is  a  crystalline  compound;  m.p.  104°,  b.p.  240°. 
With  ferric  chloride  it  gives  a  green  color,  which,  on  the  addition  of 
sodium  carbonate  or  acetate,  turns  violet.  This  color  test  is  charac- 
teristic of  ortho-di-hydroxy  compounds.  It  reduces  Fehling's  solution. 


6l8  ORGANIC  CHEMISTRY 

Resorcinol,  i-3-Di-hydroxy  Benzene. — The  meta-di-hydroxy  ben- 
zene is  known  as  resorcinol  or  resorcin.  It  is  also  obtained  from  plant 
resins  by  alkali  fusion.  Synthetically  it  is  prepared  from  phenol 
meta-sulphonic  acid  and  from  meta-chlor  phenol.  In  the  case  of 
chlor  phenol  the  para  compound  also  yields  meta-di-hydroxy  benzene 
due  to  position  rearrangement. 

Resorcinol  is  a  crystalline  compound;  m.p.  119°,  b.p.  276.5°.  It 
reduces  Fehling's  solution  like  the  ortho  compound,  but  it  differs  from 
the  latter  in  that  while  it  gives  a  color  test  with  ferric  chloride  the  color 
is  destroyed  by  adding  sodium  carbonate. 

Fluorescein. — It  is  an  important  compound  in  its  reaction  with 
phthalic  anhydride,  yielding  beautiful  dyes  known  as  fluorescein  and 
eosine.  Hydroxy  azo  compounds  formed  from  it,  however,  are  not 
valuable  as  dyes. 

Orcinol,  i -Methyl  3-5-Di-hydroxy  Benzene. — The  meta  di-hy- 
droxy  derivative  of  the  benzene  homologue  toluene,  i.e.,  i -methyl  3~5-di- 
hydroxy  benzene,  is  important  because  of  its  relation  to  the  common 
indicator  litmus.  It  is  known  as  orcinol  taking  its  name  from  a  species 
of  lichen  called  orcina  from  which  it  is  obtained  by  the  fermentation  of 
glucosides  present  in  the  lichen.  Resorcinol  being  a  similar  compound 
takes  its  name  from  the  same  source.  When  various  lichens  in  their 
young  stage  are  allowed  to  ferment,  in  the  persence  of  ammonia,  potash 
or  chalk  and  atmospheric  oxygen,  a  hydrolytic  splitting  of  the  gluco- 
sides of  the  lichen  occurs,  together  with  oxidation  and  reaction  with 
ammonia.  The  resulting  products  are  dyestuffs  termed  orceill  dyes 
from  the  principal  constituent,  orcein. 

Litmus. — One  of  the  dyes  so  obtained  is  the  indicator  litmus.  Orci- 
nol does  not  yield  fluorescein  dyes  with  phthalic  anhydride. 

Hydro-quinol,  i-4-Di-hydroxy  Benzene. — The  third  isomeric  di- 
hydroxy  benzene,  viz.,  the  para  compound,  i-4-di-hydroxy  benzene, 
is  known  as  hydro-quino  or  hydro-quinone.  The  latter  name  is 
derived  from  its  relation  to  quinone  (p.  636)  from  which  it  is  obtained 
on  reduction  and  which  it  yields  on  oxidation.  Both  hydro-quinol  and 
quinone  derive  their  names  from  the  fact  that  they  are  obtained  by  the 
oxidation  of  quinic  acid,  an  acid  derived  from  the  alkaloid  quinine. 
The  phenol  is  found  in  various  plants  or  may  be  obtained  from  them  by 
the  hydrolysis  of  glucosides  present,  e.g.,  arbutin,  which  is  a  glucoside 
hydrolyzing  into  glucose  and  hydro-quinol. 


PHENOLS    AND    THEIR.  DERIVATIVES  619 

Hydro-quinol  may  be  synthesized  by  any  of  the  general  methods. 
Of  special  interest  is  its  synthesis  by  the  electrolytic  oxidation  of  ben- 
zene. It  crystallizes  in  colorless  prisms,  m.p.  170°.  With  ferric 
chloride  it  gives  no  color  reaction,  but  is  oxidized  to  quinone,  the  same 
oxidation  occurring  in  the  air  in  alkaline  solutions.  It  reduces  Fehling's 
solution  and  its  important  use  is  as  a  reducing  agent  in  photography. 

X)H 

Tri-hydroxy  Benzenes,  C6H3^-OH 
\OH 

The  three  isomeric  tri-hydroxy  benzenes  are  all  known. 


/OH  (i) 

6nAoH  (2) 
XOH  (3) 

Pyrogallol 
i-2-3-Tri-hydroxy 
benzene 

/OH  (i) 
CeH^OH  (3) 

XOH  (5) 

Phloroglucinol 
i  -3-5-Tri-hydroxy 
benzene 

/•OH  (i) 
CeH3—  OH  (2) 

XOH  (4) 

Hydroxy  hydro-quinol 
i-2-4-Tri-hydroxy  benzene 

Only  two  of  these  will  be  considered  in  detail.  Hydroxy  hydro-quinol, 
so  named  because  it  is  the  only  possible  tri-hydroxyl  compound  derived 
from  hydro-quinol,  is  not  of  special  importance. 

Pyrogallol.  —  Pyrogallol,  the  vicinal  or  1-2  -3  -tri-hydroxy  benzene, 
is  also  called  pyro-gallic  acid  as  it  is  obtained  by  heating  gallic  acid 
which  is  a  mono-carboxy  tri-hydroxy  benzene. 

.COOH          -CO2  /OH  (i) 

C6H/  -  >  CeHAOH  (2) 

(OH)3  NOH  (3) 

Gallic  acid  Pyrogallol 

It  is  obtained  as  a  product  of  wood  distillation,  being  present  in  wood 
creosote  as  a  di-methyl  ether.  It  may  be  prepared  by  the  general  meth- 
ods of  synthesizing  phenols.  Its  most  interesting  synthesis  is  by 
the  oxidation  of  phenol  by  fusion  with  sodium  hydroxide,  but  not  with 
potassium  hydroxide.  It  is  a  white  crystalline  compound,  m.p.  132°, 
easily  soluble  in  water.  It  is  readily  oxidized  especially  when  in  alka- 
line solution.  The  chief  uses  of  it  are  due  to  this  strong  reducing 
property. 

Gas  Analysis.  —  One  use  of  it  is  in  gas  analysis  for  the  determina- 
tion of  oxygen.  When  air  or  an  oxygen  containing  gas  mixture  is 
passed  through  an  alkaline  solution  of  pyrogallol  all  of  the  oxygen  is 


620  ORGANIC  CHEMISTRY 

quantitatively  absorbed  and  the  amount  present  may  be  calculated 
from  the  diminution  of  the  original  volume  of  gas. 

Photographic  Developer. — A  second  important  use  is  as  a  reducing 
agent  in  photographic  developers.  It  also  yields  a  class  of  dyestuffs. 

Phloroglucinol. — The  symmetrical  or  i-3-5-tri-hydroxy  benzene, 
is  known  as  phloroglucinol  or  phloroglucin.  It  occurs  in  many  plants 
and  in  numerous  resins,  especially  of  fruit  trees,  where  it  is  present  in 
combination  as  a  glucoside,  phloridzin.  This  glucoside  hydrolyzes  with 
alkalies  to  glucose  and  phloretin.  Phloretin  is  a  condensation  product 
of  ortho-hydroxy  hydratropic  acid,  an  acid  related  to  the  alkaloid 
atropine  (p.  895)  and  phloroglucinol,  the  latter  being  obtained  by 
treatment  of  the  phloretin  with  alkalies.  The  phenol  is  prepared 
synthetically  from  benzene  i-3-5-tri-sulphonic  acid  by  potash  fusion 
or  from  i-3-5-tri-nitro  benzene  by  reduction  to  the  tri-amino  com- 
pound, followed  by  diazotization  and  decomposition  of  the  diazo  com- 
pound with  water.  It  may  also  be  made  by  oxidation  of  resorcinol 
or  i-3-di-hydroxy  benzene  by  fusion  with  sodium  hydroxide.  Phloro- 
glucinol crystallizes  in  plates  with  two  molecules  of  water  which  are 
lost  at  100°,  m.p.  217°.  It  is  soluble  in  water  and  has  a  sweet  taste. 
This  fact  and  its  relation  to  phloridzin  gives  the  name  to  the  compound. 
It  gives  a  color  reaction  with  ferric  chloride  and  reduces  Fehling's 
solution.  Like  pyrogallol  an  alkaline  solution  of  it  absorbs  oxygen 
from  the  air. 

Pentosan  Reagent. — With  furfural  (p.  853)  it  forms  an  insoluble 
greenish  black  phloroglucid  compound.  As  pentosans  (p.  338)  yield 
furfural  on  boiling  with  hydrochloric  acid,  phloroglucinol  is  used  as  a 
reagent  for  the  determination  of  the  furfural  obtained  and  from  this  the 
amount  of  pentosan  is  calculated  empirically.  This  is  the  official 
method  for  determination  of  pentosans  in  food  stuffs. 

Constitution.  Tautomerism. — The  constitution  of  each  of  the 
poly-phenols  which  we  have  considered  has  not  been  taken  up  because 
it  has  been  sufficiently  established  by  the  syntheses  and  reactions  as 
given.  In  the  case  of  phloroglucinol,  however,  we  have  another  case 
of  tautomerism.  Its  constitution  as  tri-hydroxy  benzene  is  established 
by  the  syntheses  given  for  it  and  the  fact  that  it  yields  tri-acyl  deriva- 
tives. Toward  other  reagents,  however,  it  acts  otherwise  than  as  a 
hydroxyl  compound.  Hydroxylamine,  H2N — OH,  which  is  the 
characteristic  reagent  for  aldehydes  and  ketones  (p.  124),  yields  a 


PHENOLS   AND   THEIR  DERIVATIVES  621 

tri-oxime  indicating  that  the  compound  is  a  tri-ketone,  i.e.,  contains 
three  carbonyl  groups  (  =  CO).  The  two  tautomeric  formulas  are, 
therefore, 

OH  O 


HO— CV       .XC— OH          O 


1^0=0 


C 
H2 

Tri-phenol  formula  Tri-ketone  formula 

Tri-hydroxy  benzene  Hexa-methylene  tri-ketone 

Phloroglucinol 

DERIVATIVES  OF  PHENOLS 

As  hydroxyl  substitution  products  possessing  both  acid  and  alcohol 
properties  the  phenols  yield  salts,  esters  and  ethers.  The  salts  and  esters 
have  been  sufficiently  considered.  The  ethers  of  phenols,  especially 
of  those  which  contain  an  unsaturated  side  chain,  include  several 
important  compounds. 

Phenol  Ethers,  Aryl  —  O—  Alkyl 

We  have  already  mentioned  the  methyl  and  ethyl  ethers  of  pTienol, 
viz.,  phenyl  methyl  ether  or  anisole  and  phenyl  ethyl  ether  or  phenetole 
(p.  612). 

Guaiacol.  —  A  phenol  ether  which  needs  more  detailed  mention  is  the 
mono-methyl  ether  of  pyrocatechinol  which  is  known  as  guaiacol.  We 
have  stated  that  with  water  in  the  presence  of  aluminium  chloride 
guaiacol  yields  pyrocatechinol  or  i-2-di-hydroxy  benzene, 


C6H4<f  •     Also  by  reduction  with  zinc  it  yields  anisole  or  phenyl 

\OH(2) 

methyl  ether,  C6H5  —  O  —  CH3.     These  two  reactions  prove  its  consti- 
tution as: 


4\ 

\0-7CH3(2) 

Guaiacol 


622  ORGANIC  CHEMISTRY 

Guaiacol  derives  its  name  from  the  fact  that  it  is  obtained  by  the  dis- 
tillation of  a  resin  known  as  guaiac.  It  is  also  similarly  obtained  from 
beech  wood.  It  yields  a  neutral  ester  with  carbonic  acid. 


-CH3 

Guaiacol  carbonate 

This  compound  possesses  medicinal  properties  and  at  one  time  was 
considered  as  a  remedy  for  tuberculosis. 

Phenols  with  Unsaturated  Side  Chain. — At  the  close  of  the  discus- 
sion of  the  mono-phenols  we  mentioned  the  fact  that  phenols  derived 
from  benzene  homologues  containing  an  unsaturated  side  chain  are 
known.  These  will  now  be  considered  briefly  in  connection  with  their 
ether  derivatives  which  are  the  more  important  compounds.  The 
hydrocarbons  of  the  benzene  series  which  contain  an  unsaturated  side 
chain  instead  of  a  saturated  one  and  which  have  been  mentioned  are 
phenyl  ethylene,  C6H5— CH  =  CH2 ;  phenyl  propenes,  C6H5— CH2— CH 
=  CH2,  C6H5— CH  =  CH— CH3,  and a/^a-phenyl  propene,  C6H5— C  = 
C — CH3.  Phenols,  i.e.,  ring  hydroxyl  substitution  products  of  these 
hydrocarbons,  are  of  special  importance  in  that  their  ether  derivatives  are 
constituents  of  some  essential  oils.  These  oils  which  are  also  known  as 
ethereal  oils  are  products  obtained  from  the  leaves,  flowers  or  fruit  of 
many  plants,  e.g.,  anis  seed  oil,  estragon  oil,  fenchel  oil,  oil  of  cloves,  bay 
oil,  oil  of  sassafras,  etc. 

Isomerism. — The  above  hydrocarbons  in  which  the  unsaturated  side 
chain  contains  more  than  two  carbon  atoms  exist  in  isomeric  forms 
depending  upon  the  position  which  the  benzene  ring  occupies  in  the 
unsaturated  chain  or,  which  is  the  same  thing,  the  position  of  the  double 
or  triple  bond  in  the  side  chain.  Thus  two  phenyl  propenes  are  known, 

C6H5— CH  =  CH— CH3      and      C6H5— CH2— CH  =  CH2 

a-Phenyl  propene  -y-Phenyl  propene 

In  the  phenols  and  phenol  ethers  derived  from  these  hydrocarbons  this 
isomerism  is  of  special  importance.  In  many  cases  one  isomer  may  be 
converted  into  the  other  by  simple  heating  with  alcoholic  potassium 
hydroxide.  In  such  a  conversion  there  is  a  shifting  of  the  position  of 
the  double  bond. 


PHENOLS   AND   THEIR  DERIVATIVES  623 

Anol  and  Anethole. — The  para  hydroxyl  derivative  of  alpha-phenyl 
propene  is  known  as  anol.  The  methyl  ether  of  anol  is  known  as 
anethole.1 

(4)  HO— C6H4— CH  =  CH— CH3  (i) 

Anol 
para-Hydroxy  a-phenyl  propene 

(4)  CH30— C6H4— CH  =  CH— CH3  (i) 

Anethole 
para-Methyoxy  a-phenyl  propene 

Anethole  is  a  constituent  of  of  anis  seed  oil. 

Chavicol  and  Estragole. — The  para  phenol  isomeric  with  anol  is 
known  as  chavicol  and  is  found  in  betel  leaf  oil.  Its  methyl  ether  is 
estragole  which  is  a  constituent  of  estragon  oil. 

(4)  HO— C6H4— CH2— CH  =  CH2  (i) 

Chavicol 
para-Hydroxy  -y-phenyl  propene 

(4)  CH3O— C6H4— CH2— CH  =  CH2  (i) 

Estragole 
para-Methoxy  -y-phenyl  propene 

Eugenole  and  Safrole. — The  chief  constituent  of  a  more  common 
essential  oil  is  eugenole  which  occurs  in  oil  of  cloves.  It  is  the  mono- 
methyl  ether  of  di-hydroxy  7-phenyl  propene  in  which  the  methoxy 
group  is  meta  and  the  hydroxyl  group  is  para  to  the  propene  chain.  It 
is  thus  a  propene  derivative  of  the  mono-methyl  ether  of  pyro-catechinol. 
The  alpha  isomer  is  known  as  iso-eugenole. 

(4)HO 

>C6H3— CH2—  CH  =  CH2(i) 

(3)CH30/ 

Eugenole 

4-Hydroxy  3 -methoxy 
7-phenyl  propene 

(4)HO 

">C6H3— CH  =  CH— CH3(i) 
(3)CH30/ 

Iso-eugenole 

4-Hydroxy  3 -methoxy 

a-phenyl  propene 

1  The  termination  ok  is  used  to  distinguish  from  the  phenol  with  the  termina- 
tion ol.  Usually  however,  the  customary  spelling  of  the  essential  oil  constituents 
is  without  the  final  e. 


624  ORGANIC  CHEMISTRY 

The  methylene  ether  corresponding  to  eugenole  is  known  as  safrole  and  is 
the  chief  constituent  of  oil  of  sassafras.    Its  alpha  isomer  is  iso-safrole. 

(4) 
s  C6H3—  CH2—  CH  =  CH2(i) 

x 


(3) 

Safrole 

Methylene  ether  of 
3-4-di-hydroxy  -y-phenyl  propene 


(4) 

> 
CH2        >C6H3—  CH  =  CH—  CHs(i) 


(3) 

Iso-safrole 

Methylene  ether  of 

3-4-di-hydroxy  a-phenyl  propene 

The  conversion  of  eugenole  into  iso-eugenole  and  of  safrole  into  iso- 
safrole  is  accomplished  by  boiling  with  alcoholic  potassium  hydroxide. 
The  oxidation  products  of  these  ethers  are  other  important  essential 
oil  constituents.  Eugenole  yields  the  corresponing  aldehyde  which  is 
known  as  vanillin,  the  chief  constituent  of  vanilla  beans  from  which 
vanilla  extract  is  made.  Safrole  by  oxidation  yields  a  compound  known 
as  piperonal  also  as  heliotropine.  It  has  the  odor  of  heliotrope  flowers 
and  is  used  as  artificial  heliotrope  essence.  These  latter  compounds 
and  also  constituents  of  other  essential  oils  will  be  considered  in  detail 
later  in  their  proper  chemical  relationship  (p.  661,  etc.). 

SUBSTITUTED  PHENOLS 

The  substituted  phenols  result  from  the  substitution  of  an  additional 
element  or  group  in  the  original  benzene  ring.  Derivatives  of  only 
the  mono-phenols  will  be  mentioned.  Considered  as  benzene  deriva- 
tives these  compounds  will  be  poly-substitution  products  and,  therefore, 
possible  of  existence  in  isomeric  forms.  We  thus  shall  have: 

Halogen-hydroxy  benzenes  or  halogen  phenols. 

Sulphonic  acid-hydroxy  benzenes         or  phenol  sulphonic  acids. 
Nitroso-  and  nitro-hydroxy  benzenes  or  nitroso  and  nitro  phenols. 
Amino-hydroxy  benzenes  or  amino  phenols. 


PHENOLS   AND   THEIR  DERIVATIVES  625 

We  may  also  have  phenols  with  an  aldehyde  group  or  with  a  carboxyl 
group  in  the  ring.  These  will  be  considered  under  hydroxy  aldehyde 
and  hydroxy  acid  compounds.  Cyanogen  may  likewise  be  the  addi- 
tional substituting  group,  but  as  such  compounds  are  nitriles  of  the 
hydroxy  acids  they  too  will  be  taken  up  later  in  connection  with  these 
acids.  We  have  then  the  four  groups  of  compounds  first  mentioned  to 
consider  at  this  time. 

General  Methods  of  Synthesis.  —  The  general  methods  of  synthesis 
are  two:  (i)  From  phenols  by  direct  substitution  of  some  other  element 
or  group  in  the  ring  of  a  phenol.  As  the  presence  of  a  side  chain  in  the 
ring,  in  the  case  of  the  homologues  of  benzene,  makes  the  compound 
more  easily  susceptible  to  the  substitution  of  other  groups,  so,  like- 
wise, the  presence  of  the  hydroxyl  group  in  the  ring  makes  further  sub- 
stitution more  easy.  Thus  nitro  phenols  and  phenol  sulphonic  acids 
are  more  easily  prepared  by  the  action  of  nitric  or  sulphuric  acid  on 
phenols  than  are  the  corresponding  derivatives  of  the  hydrocarbons 
themselves,  by  the  similar  direct  action  of  the  acids  on  the  hydrocar- 
bons. (2)  From  substituted  sulphonic  acids  or  amines.  By  starting 
with  the  necessary  substituted  sulphonic  acid,  by  fusion  with  potassium 
hydroxide  the  sulphonic  acid  group  is  replaced  by  the  hydroxyl  group 
and  the  substituted  phenol  results.  Similarly  if  a  substituted  amino 
benzene  is  diazotized  and  then  decomposed  with  water  the  diazo 
group  which  resulted  from  the  original  amino  group  is  replaced  by  the 
hydroxyl  group  and  we  obtain  the  substituted  phenol. 

/OH 
Halogen  Phenols,  C6H4<^ 

XHal. 

While  the  introduction  of  halogens  into  benzene  takes  place  only 
with  the  aid  of  carriers,  phenol  reacts  with  chlorine  or  bromine  at 
ordinary  temperatures  yielding  chlor  or  brom  phenols.  By  the  action 
of  bromine  water  on  phenol  the  product  is  tri-brom  phenol. 


C6H5-OH+3Br2        -»     C6H2 

Phenol  YBr(4) 

\Br(6) 

2-4-6-Tri-brom  phenol 

This  compound  is  a  characteristic  product  crystallizing  in  fine  needles 
and  its  formation  is  used  as  a  test  for  phenol. 

40 


626  ORGANIC  CHEMISTRY 

The  chlor  phenols  are  best  formed  by  the  action  of  sulphuryl  chloride, 
SOsC^,  on  phenol.  Iodine  does  not  act  directly  on  phenol,  but  in  the 
presence  of  hydriodic  acid,  HI,  or  mercuric  oxide,  HgO,  reaction  occurs 
and  iodine  is  substituted  in  the  ring.  The  halogen  phenols  are  more 
strongly  acid  than  phenol  itself.  Fusion  of  a  halogen  phenol  with 
alkali  replaces  the  halogen  with  hydroxyl  and  a  poly-phenol  results. 
In  this  reaction  position  rearrangement  of  the  substituting  groups 
often  takes  place.  All  of  the  five  remaining  hydrogen  atoms  of  the 
benzene  ring  in  phenol  have  been  replaced  by  chlorine  or  bromine  or  a 
mixture  of  the  three  halogens.  Many  of  the  halogen  derivatives  of 
phenol  and  also  the  salts,  esters  and  ethers  derived  from  them  are 
known,  but  are  not  of  sufficient  importance  to  be  considered  further. 
This  is  also  true  of  the  halogen  derivatives  of  the  higher  mono-phenols. 

/OH 
Phenol  Sulphonic  Acids,  C6H4 


The  sulphonation  of  phenol  takes  place  easily  on  treating  it  with 
concentrated  sulphuric  acid. 

X)H  .OH 

CeH4v  -  >     CeH4v 

X(H  +  HO)—  SO2OH  XS02OH(o)  (p) 

Phenol  Phenol  sulphonic  acid 

Phenol  sulphonic  acid  is  isomeric  with  the  sulphuric  acid  ester  of  phenol 
or  phenyl  sulphuric  acid,  the  difference  being  that  already  discussed 
as  existing  between  sulphonic  acids  and  sulphuric  acid  esters  (p.  515). 


C6H  C6H6—  O—  Sp2—  OH 

\OA-I  _  Ol-T  Phenyl  sulphuric  acid 

Phenol  sulphonic  acid 

At  ordinary  temperatures  the  sulphonation  of  phenol  yields  mostly 
the  ortho  compound  with  some  of  the  para.  At  raised  temperatures 
the  para  compound  only  is  obtained,  the  first  formed  ortho  compound 
being  converted  into  the  para.  The  meta  compound  is  not  formed  by 
direct  sulphonation  of  phenol.  As  previously  stated  (p.  522),  the  alkali 
fusion  of  di-sulphonic  acids  yields  the  di-phenols.  By  careful  fusion 


PHENOLS   AND   THEIR  DERIVATIVES  627 

at  i7O°-i8o°  it  is  possible  to  replace  only  one  of  the  sulphonic  acid 
groups  with  hydroxyl  and  in  this  way  obtain  the  phenol  sulphonic  acid. 
Thus  meta-phenol  sulphonic  acid  results  from  such  fusion  of  meta- 
benzene  di-sulphonic  acid. 

/(SOaOH(i) 

C6H/  +  K)-OH  -  >  C6H4 

XS02OH(3) 

meta-Benzene  di-sulphonic  acid  meta-Plenol  sulphonic  acid 

It  is  interesting  that  the  para  benzene  di-sulphonic  acid  also  yields 
the  meta  phenol  sulphonic  acid  due  to  position  rearrangement.  This 
same  rearrangement,  it  will  be  recalled,  occurs  in  the  stronger  fusion 
of  the  para  di-sulphonic  acid,  meta  di-phenol  being  obtained  (p.  522). 
Amino  benzene  sulphonic  acid  may  also  be  converted  into  phenol 
sulphonic  acid  by  diazotization  and  decomposition  of  the  diazo  com- 
pound with  water. 

OH 
Nitroso  Phenols,  C 


When  phenol  is  treated  with  nitrous  acid,  HO  —  NO,  the  nitroso 
group  enters  the  ring  in  the  para  position. 

OH  OH(i) 

CeH4\^  -  >         CeH4\ 

X(H  +  HO)—  NO  NO(4) 

Phenol  para-Nitroso  phenol 

The  constitution  is  proven  by  the  fact  that  the  compound  may  be  pre- 
pared from  para-nitroso  di-methyl  aniline  which  is  the  characteristic 
product  of  the  reaction  of  nitrous  acid  on  di-methyl  aniline  (p.  553). 

(CH3)2N—  C6H4(—  H  +  HO)—  NO  -  -»   (i)(CH3)2N—  C6H4—  NO(4) 

Di-methyl  aniline  para-Nitroso  di-methyl  aniline 


(N(CH3)2(i) 

C6H/  +H)—  OH       ->     C6H  +NH(CH8)» 

XNO  (4)  XNO(4) 

para-Nitroso  di-methyl  para-Nitroso  Di-methyl 

aniline  phenol  amine 


628  ORGANIC  CHEMISTRY 

Therefore  the  constitution  is 

OH 

C 


HC 


CH 


NO 

para-Nitroso  phenol 

Quinone  Oxime.  —  However,  the  same  compound  may  be  obtained 
by  a  wholly  different  reaction.  Quinone  is  a  di-ketone  derivative  of 
benzene  related  to  hydroquinol  (p.  636).  Its  constitution  by  this 
relationship  is  as  given  below.  Now  when  this  di-ketone  is  treated 
with  hydroxyl  amine  which  is  the  characteristic  reagent  for  aldehydes 
and  ketones,  yielding  oximes,  we  obtain  a  mono-oxime  as  follows: 


O 


C 

OCH 
CH 


H 


O 


CH 


(O  +  H2) 

Quinone 


N—  OH 


N—  OH 

Quinone  mono-oxime 


Now  this  mono-oxime  of  quinone  which  must  have  the  above  constitu- 
tion is  identical  with  para-nitroso  phenol. 

Pseudo  Compounds.  —  We  have  then  another  .case  of  taulomerism, 
the  compounds  in  this  case  being  termed  pseudo  compounds,  i.e.,  com- 
pounds apparently  different  but  which  exist  in  the  free  condition  in 
only  one  structural  form,  molecular  rearrangement  occurring  between 
them. 


PHENOLS   AND   THEIR  DERIVATIVES 

OH  O 


629 


CH 


NO 

para-Nitroso  phenol 


N— OH 

Quinone  mono-oxime 


Nitro  Phenols,  C6H 


OH 


NO, 


The  nitro  derivatives  of  phenols  are  even  more  easily  formed  than 
the  nitro  derivatives  of  the  hydrocarbons  which,  as  will  be  recalled, 
are  readily  formed  by  the  action  of  a  mixture  of  nitric  and  sulphuric 
acids  upon  the  hydrocarbon.  Even  with  dilute  nitric  acid  phenol 
undergoes  substitution  with  the  formation  of  a  mono-nitro  phenol 
and  with  concentrated  acid  a  tri-nitro  phenol  results. 


,OH 


C6H4<         +HO)~ N02 


C6H/ 


OH 


H20 


\ 


Phenol 


(H 


ono-Nitro 
phenol 

(o.-,  p.-) 


C6H 


OH 


OH 


N  (H3 +3HO)— N02 

Phenol 


(N02)3 

Tri-nitro  phenol 


3H20 


Mono-nitro  Phenols. — In  the  first  reaction  the  product  is  a  mixture 
of  ortho-nitro  phenol  and  para-nitro  phenol.  The  two  may  be  easily 
separated  as  the  ortho  compound  is  volatile  with  steam,  crystallizing  in 
beautiful  yellow  crystals,  while  the  para  compound  is  not  volatile, 
being  left  behind  when  the  mixture  is  distilled  with  steam.  It  is  then 
extracted  from  the  residue  by  boiling  with  hydrochloric  acid,  recrystal- 
lized  from  the  same  solvent  and  obtained  as  fine  white  needles.  The 
preparation  and  separation  of  these  two  compounds  is  a  very  satis- 
factory laboratory  exercise.  The  meta-nitro  phenol  can  not  be  pre- 


630  ORGANIC  CHEMISTRY 

pared  by  the  direct  nitration  of  phenol  but  is  prepared  by  the  diazo 
method.  Meta-nitro  amino  benzene  or  nitro  aniline,  (3)O2N — C6H4- 
— NH2(i),  is  diazotized  and  the  diazo  compound  decomposed  with 
water,  the  amino  group  being  thus  replaced  by  hydroxyl. 

NH2(i)diazotiza.  N2-Cld)  OH  (i) 

C6H/  —    C6H/  +H20 >  C6H/ 

XN02(3)      tlon  NN02     (3)  XN02(3) 

meta-Nitro  aniline  meta-Nitro  benzene  meta-Nitro  phenol 

diazonium  chloride 

Tri-nitro  Phenol.  Picric  Acid. — When  the  nitration  of  phenol  is 
effected  with  concentrated  acid  three  nitro  groups  enter  the  benzene 
ring  and  a  tri-nitro  phenol  results.  The  particular  tri-nitro  compound 
formed  is  the  symmetrical  one  and  is  known  as  picric  acid. 

OH 


O2N—  C 


:— NO2 


L  J 


N02 

Picric  acid 
i-Hydroxy  2-4-6-tri-nitro  benzene 

In  preparing  picric  acid  the  phenol  is  first  converted  into  a  mixture  of 
the  ortho-  and  para-phenol  sulphonic  acid  (p.  626) .  This  by  the  action 
of  concentrated  nitric  acid  and  heat  yields  the  tri-nitro  phenol.  The 
nitro  phenols  are  all  more  strongly  acid  than  phenol  itself.  Picric  acid 
is  a  yellow  crystalline  solid,  m.p.  122.5°,  and  has  a  distinctly  bitter 
taste.  It  forms  an  intensely  yellow  solution  in  water  and  the  salts  are 
even  more  strongly  colored. 

Dyestuff. — Picric  acid  is  a  dyestuff,  dyeing  wool  and  silk  a  bright 
yellow.  It  was  the  first  chemical  dye  to  be  used,  but  is  seldom  used 
now  except  in  connection  with  other  dyes  to  produce  certain  shades  of 
color. 


PHENOLS   AND   THEIR  DERIVATIVES  631 

Picrate  Explosives.  —  A  most  important  property  of  the  salts  of 
picric  acid,  especially  ammonium  picrate,  is  their  explosive  character. 
They  are  used  in  the  manufacture  of  certain  smokeless  powders,  e.g., 
melinite  and  liddite.  Picric  acid  itself  is  not  explosive  but  the  salts 
are  exploded  either  by  percussion  or  ignition.  Picric  acid  is  used  as 
an  antiseptic  and  alleviator  in  the  case  of  burns.  It  precipitates 
organic  bases  and  proteins  and  is  used  in  this  way  as  a  test  for  proteins. 

OH 
Amino  Phenols, 


.  The  most  important  phenol  derivatives  are  the  nitro  phenols,  which 
we  have  just  discussed,  and  the  related  amino  phenols.  The  amino 
phenols  like  the  amino  hydrocarbons  may  be  formed  by  the  reduction 
of  the  corresponding  nitro  or  nitroso  compounds. 

/OH  OH 

C.H/         +H  ->        C.H/ 

XN02  XNH2 

Nitro  phenol  Amino  phenol 

The  reduction  may  be  brought  about  either  by  means  of  tin  and 
hydrochloric  acid  or  electrolytically.  Hydroxy  azo  compounds  also 
yield  amino  phenols  on  reduction,  the  former  being  the  product  of  the 
reaction  between  a  diazonium  salt  and  a  phenol.  This  gives  an  in- 
direct method  of  preparing  amino  phenols  from  the  phenols. 

C6H5—  N—  (Cl  +  H)—  C6H4—  OH  -  —  >  C6H6—  N  =  N—  C6H4—  OH 

Phenol  Hydroxy  azo  benzene 

N 

Benzene  diazonium 
chloride 

C6H5—  N  =  N—  C6H4—  OH  +  H        -  > 

Hydroxy  azo  benzene 

(4)H2N—  C6H4—  OH(i)  +  C6H5—  NH2 

para-Amino  phenol  Aniline 

Molecular  Rearrangement  of  Hydroxyl  Amines.  —  An  important 
synthesis  of  amino  phenols  is  by  ^-molecular  rearrangement  of  hydroxyl 


632  ORGANIC  CHEMISTRY 

amine  derivatives.  Phenyl  hydroxyl  amine  undergoes  such  a  rear- 
rangement and  yields  para-amino  phenol. 

NH(OH)  OH 

I 
C  C 

HC|  ^CH     rearrangement     HCf^        ^jCH 

HcL  J  CH  HcL  J  CH 

C  C 

H  | 

Phenyl  hydroxyl  amine  XTTT 

para-Amino  phenol 

We  have  previously  stated  (p.  612)  that  mono-phenols  have  the 
hydroxyl  group  replaced  by  the  amino  group  when  they  are  treated 
with  ammonia  zinc  chloride.  Similarly,  with  greater  ease,  the  di- 
phenols  may  have  one  hydroxyl  group  replaced  by  an  amino  group 
when  heated  with  ammonia,  thus  yielding  amino  phenols.  This 
method  is  used  in  preparing  meta  amino  phenol  from  resorcinol, 
meta-di-hydroxy  benzene. 

/OH   (i)  /OH    (i) 

C6H/  +H)-NH2     -  >     C6H/ 

\OR  (3)  XNH2  (3) 

Resorcinol  meta-Amino  phenol 

The  amino  phenols  are  strongly  basic  due  to  the  fact  that  the  stronger 
basic  character  of  the  amino  group  more  than  counterbalances  the  acid 
character  of  the  phenyl  radical  of  the  phenol.  They,  therefore,  form 


, 
ammonium   salts   with   acids,   e.g.,  C6H4/  ,  hydroxy  phenyl 

XNH2.HC1 

ammonium  chloride,  hydrochloride  salt  of  amino  phenol.  The  amino 
phenols  are  easily  oxidized,  especially  in  alkaline  solution,  so  that  it  is 
impossible  to  obtain  the  free  amino  phenol  (base)  by  treatment  of  the 
salt  with  potassium  hydroxide.  To  obtain  the  free  base  from  the  salt 
we,  therefore,  use  sodium  acid  carbonate  or  sodium  sulphite. 

Photographic  Reducing  Agents.  —  The  property  of  easy  oxidation 
gives  to  the  amino  phenols  an  important  use  as  reducing  agents  in 


PHENOLS    AND    THEIR   DERIVATIVES 


633 


photographic  developers.     A  few  of  the  amino  phenol  compounds  thus 
used  in  photography  may  be  mentioned. 


Rhodinal  is  para-ammo  phenol  hydrochloride 


Amidol  is  i-3-di-amino  4-hydroxy  benzene CeH^— 

(hydrochloride  salt) 


/OH 
\NH2-HCl 

H 


H 


vNH2-HCl 
/OH 


Reducin  is  i-3-5-tri-amino  2-hydroxy  benzene 

(hydrochloride  salt) 


/OH 


d) 

(4) 

(4) 
(i) 
(3) 

(2) 

(3) 

(5) 

(5) 

Metol  is  i-methyl  2-methyl-amino  5-hydioxy  benzene..  CeHs^—CHs  (i) 

(hydrochloride  salt)  NNH(CH3)  -HC1  (2) 

Ethers. — As  phenol  compounds,  the  amino  phenols  yield  phenol 
ethers  analogous  to  phenetole  (p.  621).  These  ethers  are  themselves 
unimportant. 

Acid  Amide  Derivatives. — As  amines,  the  amino  phenols  yield,  with 
organic  acids,  compounds  of  the  add  amide  type  like  acet  amide, 
CH3 — CO — NH2.  The  compounds  first  formed  with  the  organic 
acids  are  probably  salts  analogous  to  the  hydrochloride  salt.  These, 
however,  readily  lose  water,  just  as  ammonium  acetate  does  with  more 
difficulty,  and  yield  the  acid  amide. 


-H2o 


-(H) 
(H) 
(O)OC— CH3 

Ammonium  acetate 

/OH 


H 


(i) 


--(H)  (2) 

\O)—  OC—  H 

Formic  acid  salt  of 
ortho-amino  phenol 


H2N—  OC—  CH3 

Acet  amide 


-H20 


,O 


(i) 


NH—  OC—  H   (2) 

ortho-Form-amino  phenol 


634  ORGANIC  CHEMISTRY 

This  acid  amide  compound  however,  when  the  groups  are  in  the 
ortho  positions,  loses  another  molecule  of  water  on  heating  and  yields 
an  anhydride. 

X)(H)  -H20 

C6H/  ->    C6H4 

XN(H)—  (o)c—  H  ixr 

ortho-Form-amino  phenol  Anhydride 

If,  however,  the  phenol  hydroxyl  group  is  converted  into  the  ether  the 
acid  amide  compound  is  stable  and  does  not  yield  an  anhydride. 


C6H 

XNH—  OC—  H 

ortho-Form-amino  phenol  ethyl  ether  (stable) 

The  corresponding  acetyl  derivative  is  an  important  medicinal 
snbstance. 

Phenetidine.  —  The  ethyl  ether  of  phenol  is  known  as  phenetole  and 
the  ethyl  ether  of  para-amino  phenol,  or  para-amino  phenetole  is 

X)C2H5  (i) 
similarly   named  phenetidine,   C6H4^  .     The  acetic   acid 

XNH2       (4) 

amide  of  this  compound  does  not  yield  an  anhydride  and  is  a  stable 
compound. 

Phenacetine.  —  It  is  known  as  phenacetine,   the  derivation  and 
significance  of  the  name  being  apparent  from  the  above  relationships. 

Hs  (i) 

ev 

XNH—  OC—  CH3  (4) 

Phenacetine 
i-Ethoxy  4-acet-amino  benzene 

Phenacetine  is  an  important  antiseptic  and  antipyretic  and  is  a  valuable 
medicinal  substance.  It  is  a  solid  crystalline  compound,  m.p.  135°. 
It  is  slightly  soluble  in  cold  water  and  in  70  parts  of  hot  water.  Other 
similar  derivatives  of  phenetidine  are  important.  The  one  formed 
from  glycine  or  glycocoll,  amino  acetic  acid,  CH2(NH2)  —  COOH,  is 


QUINONES  635 


known  as  phenocoll,  C6H4  /  ,  while  the  corre- 

XNH—  OC—  CH2(NH2) 
yOC2H5 

spending  lactic  acid  derivative,  C6H4  ,     is 


—  CH(QH)—  CH3 
called   lactophenine.     Still   one   more   may   be  mentioned,  viz.,  the 

X)C2H6 

carbamic    acid,     HOOC  —  NH2,  derivative,    C6H4^  , 

^NH—  OC—  NH2 

which  is  called  dulcin  and  is  a  sweet  substance  two  hundred  times  as 
sweet  as  cane  sugar,  but  not  as  sweet  as  saccharin  (p.  712). 

Dyes.  —  The  amino  phenols  are  also  important  in  connection  with 
dyestuffs.  Para-amino  phenol  is  itself  used  in  dyeing  leather,  but  in 
most  cases  the  amino  phenols  or  their  derivatives  are  intermediate 
products  in  the  formation  of  compounds  used  as  dyes;  in  particular 
certain  groups  of  azo  dyes  and  those  known  as  rhodamine  dyes. 

Azo  phenols  which  are  of  course  the  same  as  hydroxy  azo  compounds 
(p.  576),  azoxy  phenols,  hydrazo  phenols,  phenol  hydrazines  and  di- 
azo  phenols  are  all  known  either  as  phenols  or  as  phenol  ethers.  The 
last  group  is  interesting  historically  as  the  first  diazo  compound  made 
by  Griess  was  di-nitro  phenol  diazonium  chloride, 


(NO2)2  =  C6H2^N— Cl 

III 
N 

QUINONES 

Having  now  considered  those  hydroxyl  substitution  products  of 
benzene  and  its  homologues  in  which  the  substitution  is  in  the  ring, 
we  should  next  take  up  the  second  general  class  of  hydroxyl  substitu- 
tion products,  viz.,  those  in  which  the  substitution  is  in  the  side  chain, 
i.e.,  the  true  alcohols.  Before  we  take  up  these  compounds,  however, 
it  is  best  to  consider  here  a  group  related  to  the  phenols  and  concerning 
the  constitution  of  which  there  is  still  some  controversy. 


636 


ORGANIC  CHEMISTRY 


Quinone.  —  The  chief  representative  of  this  group  is  a  substance  by 
the  name  of  quinone,  or  more  definitely  benzoquinone,  which  has  the  com- 
position C6H4O2.  It  will  be  recalled  that  hydroquinone,  which  is  the 


, 

para-di-hydroxy  benzene,  C6H4<^  ,  is  made,  as  its  name  indi- 

OH(4) 

cates,  by  the  reduction  of  quinone.  This  fact  together  with  the  com- 
position of  quinone  leads  to  the  view  that  quinone  is  related  to  benzene 
in  that  two  of  the  benzene  hydrogens,  para  to  each  other,  are  replaced 
by  two  oxygen  atoms.  These  two  oxygens  on  reduction  are  converted 
into  two  hydroxyl  groups  in  hydro-quinone. 

Ketone  or  Per-oxide.  —  Two  different  constitutional  formulas  are 
possible  in  accordance  with  such  a  relationship,  viz.,  a  ketone  formula 
and  a  per-oxide  formula  as  follows: 


O- 


CH 

Quinone 
CH  HC 


C 

O 


O 

Ketone  formula 


O 


Per-oxide  formula 


In  the  ketone  structure  the  two  oxygens  are  united  directly  to 
carbon  as  the  carbonyl  or  ketone  group,  =C  =  O,  whereas  in  the  per 
oxide  structure  they  are  united  to  the  carbons  by  a  single  bond,  the 
other  valence  of  the  oxygens  mutually  satisfying  each  other  as  in 
per-oxides. 

In  order  to  make  the  ketone  formula  possible  in  accordance  with  the 
structure  of  the  benzene  ring  it  is  necessary  to  consider  the  double  bonds 
as  changing  or  oscillating  to  the  positions  indicated  in  the  above  form- 
ula. When  reduction  to  hydro-quinone  occurs  the  double  bonds 
oscillate  back  to  their  original  position. 


QUINONES 


637 


OH 


+  Hs 


HC 
HC 


v^ 

O 


CH 
CH 


Quinone 


OH 

Hydro -quinone 


Such  oscillation  of  the  double  bonds  of  the  benzene  ring  is  one  of  the 
assumptions  in  connection  with  the  Kekule  benzene  formula  as  re- 
ferred to  when  we  were  discussing  the  constitution  of  benzene  (p.  474). 
The  conversion  of  a  compound  with  the  per-oxide  formula  into 
hydro-quinone  does  not  necessitate  any  oscillation  of  the  double  bonds 
but  simply  the  breaking  of  the  union  between  the  two  oxygen  atoms 
with  their  reduction  to  hydroxyl. 


O 


HC 


Cr 

L        JCH 


O 


,    OH 


Quinone 


L  J 


OH 

Hydro-quinone 


Oximes. — Evidence  in  favor  of  the  ketone  structure  is  that  quinone 
undergoes  the  characteristic  aldehyde  or  ketone  reaction  with  hydroxyl 
amine  forming  oximes.  Furthermore,  it  forms  both  a  mono-  and  a 
di-oxime. 


CH; 


Acetone 
Ketone 


CH 


C=(O+H2)N— OH 


C  =  N— OH+H20 


CH£ 

Acet-oxime 

Ketoxime 


638 


0  +  H2NOH 


O+H2NOH 

Quinone  mono-oxime 


N— OH 

Quinone  di-ozime 


From  this  it  would  appear  that  the  two  oxygen  atoms  in  quinone  are 
each  in  the  carbonyl  grouping  and  are  independent  of  each  other. 
Another  fact  in  favor  of  the  ketone  structure  is  that  quinone  forms 
di-  and  tetra-halogen  addition  products  but  not  penta-  and  hexa-  com- 
pounds. 


O 


O 


cHBr 


O 

Tetra-bromide 

If  the  per-oxide  structure  is  the  true  one  it  would  seem  possible  to  form 
penta-  and  hexa-brom  addition  products  also. 

Benzo-quinone. — Benzoquinone,  or  more  commonly,  simply  qui- 
none, is  the  most  common  and  important  of  the  quinones  derived  from 
benzene.  Other  important  quinones  will  be  met  with  when  we 
study  derivatives  of  the  more  complex  hydrocarbons  napthalene  and 
anthracene.  Benzoquinone  is  the  one  we  have  used  as  our  example  in 
the  above  discussion  and  it  is  the  para-di-keto  benzene.  It  was  first 
obtained  by  the  oxidation  of  quinic  acid,  which  in  turn  was  obtained 
from  quinine,  hence  its  name.  It  may  also  be  prepared  by  oxidizing 


QUINONES  639 

hydroquinone  or  aniline.  It  is  a  crystalline  compound,  volatile  with 
steam,  forming  long  yellow  prisms  which  sublime  as  golden-yellow 
needles.  It  has  a  peculiar  penetrating  odor. 

Ortho-quinone. — Corresponding  to  the  common  benzoquinone 
which  is  the  para  compound,  there  are  known  derivatives  of  the 
ortho-benzoquinone.  In  this  compound,  as  represented  by  theketone 
formula,  no  oscillation  of  the  double  bonds  of  the  benzene  ring  is 
necessary. 


i    r° 

HC" 

C 
H 

Ortho-benzoquinone 

DERIVATIVES  OF  QUINONES 

Chloranil. — We  have  spoken  of  the  fact  that  halogan  derivatives  of 
quinones  are  formed  as  addition  products,  the  di-  and  tetra-products 
being  known.  The  halogens  form  other  derivatives  also  in  which  the 
halogen  is  substituted  for  hydrogen  of  the  benzene  ring.  These  are 
true  substituted  quinones.  The  tetra-chlor  quinone,  C6C14O2,  is 
known  as  chlor-anil  and  is  formed  when  aniline  or  phenol  is  treated 
with  potassium  chlorate  and  hydrochloric  acid. 

Chloranilic  Acid. — Hydroxyl  substitution  products  of  quino  e  are 
important  as  they  yield  salts  with  bases  which  are  intensely  colored 
and  therefore  valuable  as  dyes.  The  most  important  one  of  these 
compounds  is  a  di-hydroxyl  product  of  a  quinone  related  to  anthracene 
and  known  as  alizarin.  A  mixed  chlorine  and  hydroxyl  substitution 
product  is  the  di-chlor  di-hydroxy  quinone.  It  is  chloranil  in  which 
two  of  the  chlorine  atoms  have  been  replaced  by  hydroxyl  groups,  and 
is  known  as  chloranilic  acid. 


640  ORGANIC  CHEMISTRY 

O 


Cl—  CXXCOH     Chloranilic  acid 

3-6-Di-chlor  2-5-di- 
HO—  cl  JcCl       hydroxy  quinone 


O 

Quinone  Oximes. — The  most  interesting  of  the  derivatives  of 
quinones  are  the  oximes.  As  stated  in  the  discussion  of  the  ketone 
structure  for  quinones  one  of  the  proofs  for  this  constitution  is  the  fact 
that  benzoquinone  forms  both  a  mono-and  a  di-oxime  when  treated 
with  hydroxy  1-amine.  The  mono-  oxime  of  benzoquinone  would  have 
the  structure  as  written  below  and  as  given  on  page  638.  Now  as 
previously  mentioned,  (p.  628),  para-nitroso  phenol,  which  is  made  by 
the  action  of  nitrous  acid  upon  phenol  and  the  constitution  of  which  is 
established  by  other  methods  of  synthesis,  (p.  627),  proves  to  be  one 
and  the  same  compound  with  this  mono-oxine  of  para -benzoquinone, 
the  constitution1  of  which  is  likewise  established  by  the  above  reaction 
of  hydro'xyl  amine  upon  quinone.  This  is  explained  by  a  rearrange- 
ment as  shown  in  the  following: 

N— OH  OH 


ICH 
c 


O  NO 

Mono -oxime  of  para-Nitroso  phenol 

para-Benzo  quinone 

Now  the  following  facts:  (i)  the  oxime  itself  is  not  known  as  distinct 
from  para-nitroso  phenol,  (2)  there  are  known  both  ethers  and  esters 


AROMATIC    ALCOHOLS  641 

derived  from  it,  (3)  we  do  know  the  corresponding  di-oxime;  indicate 
that  the  mono-oxime  of  benzo-quinone  is  really  formed,  but  that  either 
it  or  the  para-nitroso  phenol  undergoes  a  rearrangement  into  the  other 
form.  This  is  a  peculiar  case  of  tautomerism  as  only  one  compound 
is  known  which  may  be  prepared  by  two  entirely  different  sets  of 
reactions.  Such  compounds  are  known  as  pseudo  compounds. 

Further  discussion  of  these  compounds- is  unnecessary  in  this  study, 
but  the  salient  points  have  been  brought  out  as  well  as  the  relation  of 
the  quinones  to  several  other  classes  of  compounds. 

B.  AROMATIC  ALCOHOLS 

(Hydroxyl  in  the  Side  Chain) 

MONO-HYDROXY  COMPOUNDS 

Turning  now  to  the  second  class  of  hydroxyl  substitution  products, 
the  true  alcohols,  we  must  recognize  the  essential  difference,  viz.,  that  in 
them  the  hydroxyl  group  is  substituted  in  the  side  chain  whereas  in 
phenols  it  is  in  the  ring.  Thus  toluene,  the  first  benzene  hydrocarbon 
containing  a  side  chain,  will  yield  both  a  phenol  and  an  alcohol  the 
two  being  isomeric  compounds. 

CH3  CH2OH 


—OH 


cLJ, 


HCk          ^CH  HCX  JCH 

C^ 
H  H 

ortho-Cresol  Benzyl  alcohol 

Phenol  Alcohol 

The  side  chain  hydroxyl  compounds  are  true  alcohols  in  every  respect, 
in  properties,  reactions,  methods  of  synthesis  and  derivatives.  They 
yield,  therefore,  both  ethers  and  esters.  As  alcohols  they  are  of  several 
kinds  depending  upon  the  character  of  the  alcoholic  side  chain  and 
are  exactly  analogous  to  the  different  classes  of  aliphatic  alcohols. 

Primary,  Secondary,  Tertiary. — In  the  first  place  they  may  be  either 
primary,  secondary,  or  tertiary  according  to  the  position  of  the  hydroxyl 

41 


642  ORGANIC  CHEMISTRY 

group  in  the  side  chain  when  this  side  chain  contains  more  than  one 
carbon  group,  e.g.; 

C6H5— CH2— CH2— CH2OH      C6H5— CH2— CH(OH)— CH3 

Phenyl  propyl  alcohol  Phenyl  iso  propyl  alcohol 

3-Phenyl  propanol-i  i -Phenyl, propanol-2 

Primary  Secondary 

CH3 

C6H5— C— OH 

I 
CH3 

2 -Phenyl  propanol-2 

Tertiary 

Benzyl  alcohol  or  phenyl  methyl  alcohol  given  above  can,  of  course, 
exist  only  as  a  primary  alcohol  there  being  only  one  carbon  group  in  the 
side  chain.  Like  the  aliphatic  alcohols,  the  primary  yield  aldehydes 
and  then  acids  on  oxidation,  the  secondary  yield  ketones  and  the  terti- 
ary break  down. 

Saturated  and  Unsaturated. — Again  as  alcohols  they  may  be  either 
saturated  or  unsaturated,  corresponding  to  the  two  classes  of  benzene 
homologues,  e.g.; 

C6H5— CH2— CH2— CH2OH         C6H5— CH  =  CH— CH2OH 

3-Phenyl  propanol-i  3-Phenyl  A2-propenol-i 

Grignard  Synthesis. — The  most  important  method  for  synthesizing 
aromatic  alcohols  is  by  the  Grignard  reaction,  with  magnesium  alkyl 
or  aryl  halides  (p.  77).  The  one  given  as  an  example  of  a  tertiary 
aromatic  alcohol  may  be  prepared  by  the  action  of  magnesium  phenyl 
bromide,  C6H5 — Mg — Br,  upon  acetone. 

CH3  CH3 

I  I 

CH3— C  =  O  +  C6H5— Mg— Br— >CH3— C— (OMgBr  +  H)— OH 


Acetone  Phenyl  magnesium 

bromide 


C6H5 
CH3 

CH3— C— OH  +  BrMgOH 


C6H5 

2 -Phenyl  propanol-2 


AROMATIC   ALCOHOLS  643 

By  the  Grignard  synthesis  ketones  thus  always  yield  tertiary  alcohols. 
Aldehydes  similarly  always  yield  secondary  alcohols. 

H  H 

CH3—  C  =  0  +  C6H5—  Mg—  Br  -  >CH3—  C—  (OMgBr  +  H)—  OH 

Acet  adehyde 


H 

—  »         CH3—  C—  OH  +  BrMgOH 
CeHs 

i-Phenyl  ethanol 

Tertiary  aromatic  alcohols  are  also  prepared  by  the  Grignard  reaction 
from  esters  or  acid  chlorides  of  aromatic  acids. 

OC2H5  (OC2H5  +  1—  Mg)—  CH3 

I  I 

C6H5—  C  =  0  +  CH3—  Mg—  I     -  >     C6H5—  C—  OMgl    —  > 

Ethyl  benzoate 

CH3 
CH3  CH3 

I  I 

-  >     C6H5—  C—  (OMgl  +  H)—  OH     -  >    C6H5—  C—  OH 

I  I 

CH3  CH3 

2-Phenyl  propanol-2 

Cl  (Cl  +  I—  Mg)CH3 

I  I 

C6H5—  C  =  0  +  CH3—  Mg—  I       -»     C6H6—  C—  OMgl  -^ 

Benzoyl  chloride 

CH3 
CH3  CH3 

-  >     C6H5—  C—  (OMgl  +  H)—  OH    -  >     C6H5—  C—  OH 

I  I 

CH3  CH3 

2-Phenyl  propanol-2 


644  ORGANIC  CHEMISTRY 

As  in  the  Grignard  reaction  we  may  use  any  aliphatic  aldehyde,  ketone, 
ester  or  acid  chloride,  or  an  aryl  compound  of  the  same  type;  and  also, 
we  may  use  either  alkyl  magnesium  halides  or  aryl  magnesium  halides; 
the  synthesis  makes  possible  the  preparation  of  practically  any  desired 
secondary  or  tertiary  alcohol  either  aliphatic  or  aromatic.  Also  if 
formaldehyde,  in  the  form  of  its  polymer,  tri-oxy  methylene,  is  used  in 
the  second  reaction  we  will  obtain  primary  alcohols.  In  the  third 
reaction  formic  acid  esters  yield  secondary  instead  of  tertiary  alcohols. 
These  syntheses  of  alcohols  by  the  Grignard  reaction  give  us  an  idea  of 
its  importance  in  synthetic  work. 

While  the  preceding  syntheses  are  the  most  important  the  simplest 
synthesis  of  aromatic  alcohols  is  from  the  side  chain  hologen  substitution 
products  by  treatment  with  silver  hydroxide,  potassium  hydroxide  or 
even  by  boiling  with  water. 

C6H6— CH2— Cl  +  H— OH        >        C6H6— CH2— OH 

Benzyl  chloride  Benzyl  alcohol 

Benzyl  Alcohol. — The  simplest  aromatic  alcohol  is  the  hydroxyl 
derivative  of  toluene  and  is  known  as  benzyl  alcohol,  C6H5 — CH2 — OH. 
The  radical,  (C6H5 — CH2 — ),  is  termed  benzyl  as  in  the  alcohol  and 
chloride  above.  The  alcohol  occurs  as  an  ester  in  Peru  balsam,  in 
storax,  a  resin  obtained  from  a  plant  styrax,  and  in  Tolu  balsam  from 
which  the  mother  hydrocarbon  toluene  derives  its  name.  On  hydro- 
lysis of  the  balsam  benzyl  alcohol  is  obtained.  It  is  a  liquid,  b.p.  206.5°, 
slightly  soluble  in  water  and  soluble  in  alcohol  or  ether.  It  may  be 
prepared  by  those  syntheses  just  given  which  yield  primary  alcohols. 
It  may  also  be  prepared  by  the  reduction  of  the  corresponding  aldehyde, 
known  as  benzole  aldehyde  or  benzaldehyde  (p.  655).  On  oxidation 
it  yields  the  aldehyde  and  then  an  acid,  benzole  acid. 

C6H5— CH2— OH    _J1°     C6H6— CHO    lL°      C6H5— COOH 

Benzyl  alcohol  Benzaldehyde  Benzoic  acid 

Strong  reducing  agents  reduce  it  to  the  hydrocarbon  toluene. 
C6H5— CH2— OH  +  HI  +  P        >        C6H5— CH3 

Benzyl  alcohol  Toluene 

It  yields  both  esters  and  ethers,  e.g.; 

C6H5— CH2— O— OC— CH3,    Benzyl  acetate. 
C6H5— CH2— O— CH3,  Benzyl  methyl  ether. 


AROMATIC  ALCOHOLS  645 

Homologues. — The  homologues  of  benzyl  alcohol  result  from  sub- 
stitution of  the  hydroxyl  group  in  one  of  the  methyl  groups  of  xylene, 
mesitylene,  etc.,  or,  as  in  the  examples  previously  given  of  secondary 
and  tertiary  aromatic  alcohols,  by  the  substitution  of  hydroxyl  in  a 
poly-carbon  side  chain  either  saturated  or  unsaturated.  These  need 
not  be  discussed  further  except  to  mention  that  both  phenyl  propanol, 
C6H5— CH2— CH2— CH2OH,  and  phenyl  propenol,  C6H5— CH  =  CH— 
CH2OH,  are  also  found  as  cinnamic  acid  esters  in  storax. 

Cinnamic  Alcohol. — The  latter  alcohol  yields  an  unsaturated  aro- 
matic acid  known  as  cinnamic  acid  (p.  697),  and  the  alcohol  is  thus 
known  as  cinnamic  alcohol.  Phenyl  ethyl  alcohol,  C6H5 — CH2 — CH2 
— OH,  is  a  constituent  of  oil  of  rose  and  has  the  characteristic 
odor  of  roses. 


POLY-HYDROXY  COMPOUNDS 

Aromatic  Glycols. — As  we  have  poly-phenols  which  contain  more 
than  one  hydroxyl  group  in  the  ring  so  we  may  have  poly-alcohols 
containing  side  chains  in  which  more  than  one  hydroxyl  group  is 
present.  Those  with  two  hydroxyl  groups  will  be  phenyl  derivatives 
of  the  glycols  the  di-hydroxy  aliphatic  alcohols. 

CH3— CH2— OH  C6H5— CH2— CH2OH 

Ethyl  alcohol  Phenyl  ethyl  alcohol 

CH2(OH)— CH2— OH  C6H5— CH(OH)— CH2— OH 

Glycol  Phenyl  glycol 

While  these  compounds  are  not  of  especial  importance  another  class  of 
di-hydroxyl  compounds  does  contain  some  important  members. 

Phenol  Alcohol. s — Just  as  the  aromatic  alcohols  are  isomeric  with 
certain  phenols,  e.g.,  benzyl  alcohol  and  the  cresols,  so  a  di-hydroxyl 
compound  derived  from  phenyl  ethane,  in  which  one  hydroxyl  group 
is  in  the  side  chain  and  the  second  one  is  in  the  ring,  is  isomeric  with 
phenyl  glycol. 

CH2— CH2— OH 
C6H5— CH(OH)— CH— OH          C6H/ 

Phenyl  glycol  OH 

Hydroxy  phenyl  ethyl  alcohol 


646  ORGANIC  CHEMISTRY 

Salicylic  Alcohol.  —  Such  a  compound  is  a  mixed  phenol  and  aromatic 
alcohol.  The  corresponding  derivative  of  methyl  alcohol,  viz.,  the 
ortho  compound,  occurs  combined  with  glucose  as  a  glucoside  known 

/OH  (i) 

C6H/ 

XCH2—  OH(2) 

Salicylic  alcohol  « 

i-Hydroxy  2-Hydroxy-methyl  benzene 

as  salicin  which  is  presertt  in  willow  bark.  As  we  shall  find  later  this 
alcohol  is  directly  related  to  salicylic  acid  which  it  yields  on  oxidation. 
It  is  thus  known  also  as  salicylic  alcohol. 

Coniferyl  Alcohol.  —  If  two  hydroxyl  groups  are  present  in  the  ring 
and  one  in  the  side  chain  we  will  have  a  mixed  diphenol  and  aromatic 
alcohol.  Such  an  alcohol,  in  which  one  phenol  hydroxyl  is  in  the  form 
of  a  methyl  ether,  and  the  side  chain  is  the  propenol  unsaturated  chain, 
is  known  as  coniferyl  alcohol. 

/OH  (i) 

C6H3A)CH3  (2) 

XCH=CH—  CH2OH(4) 

Coniferyl  alcohol 

Coniferyl  alcohol  like  salicylic  alcohol  occurs  as  a  glucoside  in  plants, 
in  the  cambium  sap  of  conifer  trees.  The  glucoside  is  known  as  coni- 
ferin.  On  hydrolysis  these  glucosides  yield  the  alcohols. 

Thio-Phenols  and  Aromatic  Mercaptans 

Sulphur  analogues  of  phenols  and  aromatic  alcohols  are  known,  e.g., 
C6H5—  SH  C6H5—  CH2—  SH 

Thio-phenol  Benzyl  mercapatan 

Phenyl  methyl  mercaptan 

Both  of  these  compounds  yield  sulphides  or  thio-ethers.  Thio-phenol 
by  the  diazo  reaction  yields  di-phenyl  sulphide,  C6H5  —  S  —  C6H5, 
di-phenyl  thio-ether  and  benzyl  mercaptan  yields  di-benzyl  sulphide, 
C6H5—  CH2—  S—  CH2—  C6H5,  di-benzyl  thio-ether.  These  sulphides 
on  oxidation  yield  sulphones  (p.  526). 


—  S  —  CeHs        -  >         CeHs  —  SO2  —  CeH 

Di-phenyl  sulphide  Di-phenyl  sulphone 


VIII.  AROMATIC  ALDEHYDES  AND  KETONES 

In  considering  the  aromatic  aldehydes  and  ketones  and  later  the 
aromatic  acids  it  should  be  emphasized  that  the  relationships  discussed 
in  Part  I  (p.  129)  between  alcohols,  aldehydes,  ketones  and  acids  are 
general  and  apply  just  as  truly  to  the  aromatic  compounds  as  to  the 
aliphatic.  The  class  characteristics  of  alcohols,  aldehydes,  ketones 
and  acids  are  the  same  in  both  series.  Thus  the  primary  alcohols, 
on  oxidation,  always  yield  first  aldehydes  and  then  acids,  while  the 
secondary  alcohols  yield  ketones. 

General  and  specific  formulas  expressing  these  relationships  are  as 
follows: 

R— CH2OH  — >        R— CHO  — >        R— COOH 

Primary  alcohol  Aldehyde  Acid 

CH3— CH2OH        >        CH3— CHO       >        CH3— COOH 

Ethyl  alcohol  Acet  aldehyde  Acetic  acid 

Aliphatic 

C6H5— CH2OH        >        C6H5— CHO    >     C6H5— COOH 

Benzyl  alcohol  Benzaldehyde  Benzoic  acid 

Aromatic 

R— CHOH— R        >  R— CO— R 

Secndary  alcohol  Ketone 

CH3— CHOH— CH3        >        CH3— CO— CH3 

Propanol-2  Acetone 

Aliphatic 

C6H5— CHOH— CH3         >        C6H5— CO— CH3 

l-Hydroxy  1-phenyl  ethane  Aceto  phenone 

In  aliphatic  ketones  we  have  both  simple  or  symmetrical  ketones, 
in  which  the  two  radicals  (R)  are  alike,  and  mixed  or  unsymmetrical 
ketones,  in  which  the  two  radicals  are  unlike.  In  aromatic  ketones  also, 
the  two  radicals  may  be  alike  and  both  aromatic,  e.g.,  C&H.5 — CO — CeHs, 
di-phenyl  ketone  or  benzophenone,  which  is  a  symmetrical  aromatic 
ketone.  They  may  be  unlike  and  both  aromatic,  e.g.,  phenyl  tolyl 

647 


648  ORGANIC  CHEMISTRY 

ketone,  C6H5 — CO — C6H4 — CH3,  which  is  unsymmetrical  but  wholly 
aromatic.  Also  one  radical  may  be  aromatic  and  the  other  aliphatic, 
e.g.,  C6H5 — CO — CH3,  phenyl  methyl  ketone  or  aceto  phenone,  which 
is  a  mixed  aromatic-aliphatic  ketone  also  unsymmetrical.  This  latter 
is  the  type  of  aromatic  ketones  related  to  the  more  common  aromatic 
secondary  alcohols. 

Synthesis  From  Alcohols. — The  general  methods  of  synthesis  of 
aromatic  aldehydes  and  ketones  are  several.  The  aldehydes  may  be 
prepared  by  the  direct  oxidation  of  the  corresponding  primary  alcohol, 
usually  with  dilute  nitric  acid,  e.g., 

C6H5— CH2OH  +  O        >        C6H5— CHO 

Benzyl  alcohol  Benzaldehyde 

Conversely,  as  previously  stated,  the  aldehydes  on  reduction  yield 
the  primary  alcohols  and  in  the  case  of  benzaldehyde,  which  is  a  com- 
monly occurring  substance  in  oil  of  bitter  almonds,  this  method  is 
used  in  the  preparation  of  the  alcohol.  In  the  case  of  the  secondary 
alcohols  oxidation  to  ketones  is  not  easily  accomplished  but  the  reverse 
reaction,  the  reduction  of  the  ketones  to  secondary  alcohols  does  take 
place  with  ease. 

C6H5— CHOH— CH3          iJE          C6H5— CO— CH3 

l-Hydroxy  1 -phenyl  ethane  Phenyl  methyl  ketone 

Aceto  phenone 

From  Halogen  Substitution  Products. — Other  common  methods  for 
the  preparation  of  the  aldehydes  are  those  from  the  halogen  substitution 
products  of  the  benzene  homologues  where  the  halogen  is  substituted 
in  the  side-chain. 

The  di-halogen  derivative  of  toluene  of  the  class  just  mentioned,  viz., 
CtiH5 — CHC12,  is  known  as  benzal  chloride  because  it  yields  benzalde- 
hyde when  boiled  with  water  as  follows: 

C6H6— CH(C12~+  H2)O        >        C6H5— CHO  +  2HC1 

Benzal  chloride  Benzaldehyde 

In  some  cases  this  reaction  takes  place  with  water  alone  but  usually 
some  other  substance  is  present;  e.g.,  calcium  hydroxide  or  carbonate, 
potassium  hydroxide,  metallic  iron  or  iron  salts;  which  actsasacatalizer. 
The  mono-chlorine  derivative  of  toluene  and  other  benzene  homologues 
may  also  be  used  for  preparing  the  aldehydes.  In  this  case  the  reaction 
is  in  two  steps,  first,  reaction  with  water  yielding  the  alcohol,  and  second, 


AROMATIC   ALDEHYDES    AND    KETONES  649 

oxidation  to  the  aldehyde.     The  reagent  used  is  usually  dilute  nitric 
acid  or  a  solution  of  lead  nitrate. 

C6H5—  CH2(C1  +  H)  OH        -  >        C6H5—  CH2OH  +  HC1 

Benzyl  chloride  Benzyl  alcohol 


C6H5-CH2OH  +  O 

Benzyl  .  Benzaldehyde 

alcohol 

From  Hydrocarbons.  —  An  interesting  method  sometimes  applicable 
for  the  preparation  of  aromatic  aldehydes  is  from  the  hydrocarbons  by 
means  of  the  Friedel-Craft  reaction,  as  modified  by  Gattermann  and 
Koch  with  carbon  monoxide  and  hydrochloric  acid  in  the  presence  of 
CuCl.  In  this  reaction  formyl  chloride,  which  is  unknown  in  the  free 
condition,  is  probably  first  formed  by  the  union  of  the  carbon  monoxide 
and  hydrochloric  acid. 

,0 

H—  Cl  +  C  =  O  —  >        H—  C/ 

XC1 

Formyl  chloride 

The  hydrocarbon  then  reacts  with  the  formyl  chloride  in  the  pres- 
ence of  CuCl  as  in  the  Friedel-Craft  reaction  with  the  elimination  of 
hydrochloric  acid  as  follows  : 

O 
C6H5(H  +  Cl)C<f  ~*        C6H5—  CHO  +  HC1 

Benzene  H  Benzaldehyde 

Formyl  chloride 

This  method  is  applicable  in  preparing  ketones  if  instead  of  formyl 
chloride  (CO  +  HC1)  an  acid  chloride  is  used  as  follows: 

C6H5(H  +  C1)OC—  CH3        -  >        C6H5—  CO—  CH3  +  HC1 

Benzene  Acetyl  chloride  Phenyl  methyl  ketone] 

C6H5(H  +  C1)OC—  C6H5        -  >        C6H5—  CO—  C6H5  +  HC1 

Benzene  Benzoyl  chloride  Di-phenyl  ketone 

From  acids.  —  A  general  method  of  synthesis  of  both  aromatic 
aldehydes  and  ketones  is  from  the  calcium  salts  of  acids.  The  reaction 
is  of  the  same  nature  as  that  which  takes  place  in  the  like  synthesis  of 
aliphatic  aldehydes  and  ketones  (Part  I,  p.  133).  To  obtain  the  alde- 
hyde the  calcium  salt  of  formic  acid  is  heated  with  the  calcium  salt  of 
the  aromatic  acid. 


650  ORGANIC  CHEMISTRY 

Calcium  benzoate  C6H5—  CO(O—  Ca)(O—  OC)—  C6H5 

I 

Calcium  formate      H—  (COO—  )  Ca—  O)OCH 

C6H5—  C  =  0  +  0=C—  C6H5  +  2CaCO3 

H  H 

Benzaldehyde 

When  the  calcium  salt  of  one  aromatic  acid  alone  is  heated  a  sym- 
metrical di-aromatic  ketone  results  as  follows  : 
C6H5-CO(0  C6H, 

^>Ca  +  heat         —  »  ^>C  =  O  +  CaCO3 

C6H5—  (COOX  CeW 

Calcium  benzoate  Di-phenyl  ketone 

The  mixed  calcium  salts  of  two  different  aromatic  acids  will  yield  an 
unsymmetrical  di-aromatic  ketone. 

If  a  mixture  of  the  calcium  salt  of  an  aromatic  acid  and  the  calcium 
salt  of  an  aliphatic  acid  is  used  the  ketone  resulting  is  a  mixed  aromatic 
aliphatic  compound. 
Calcium  benzoate  C6H5—  CO(O—  Ca)—  (O)OC—  C6H5 


, 

<( 
X 


Calcium  acetate       CH3—  (COO—  )—  (Ca—  OOC)—  CH3 

CeHs. 

^>CO  +  OC< 
CH/  CH3 

Phenyl  methyl  ketone 

By  this  last  reaction  the  product  will  not  be  a  single  compound  but  will 
consist  of  a  mixture  of  phenyl  methyl  ketone,  di-phenyl  ketone  and  di- 
methyl ketone  as  both  of  the  two  preceding  reactions  take  place. 

Reactions.  —  The  general  properties  and  reactions  of  the  aromatic 
aldehydes  and  ketones  are  like  those  of  their  aliphatic  relatives.  The 
aldehydes  are  easily  oxidized  to  acids  and  reduce  ammoniacal  silver 
nitrate  solution.  Both  aldehydes  and  ketones  are  easily  reduced  to 
alcohols.  The  aldehydes  form  addition  products  with  sodium  bisul- 
phite and  with  hydrogen  cyanide.  With  ammonia,  however,  they  do 
not  form  addition  products  but  react  with  the  elimination  of  water  and 
the  formation  of  a  condensation  product  which  is  a  derivative  of  two 
molecules  of  ammonia. 


3C6H5—  CHO  +  2NH3         -  >         (C6H5—  CH  =  )3N2  +  3H2O 

Benzaldehyde  Hydro  benzamide 


AROMATIC   ALDEHYDES   AND   KETONES  651 

The  resulting  compounds  are  known  as  hydramides  and  from  benzalde- 
hyde,  as  above,  the  compound  formed  is  hydro  benzamide. 

Polymerization. — The  characteristic  property  of  aldehydes  to 
polymerize  (Part  I,  p.  117)  is  true  of  the  aromatic  aldehydes  also  but 
the  reaction  takes  place  in  an  entirely  different  manner  than  in  the 
aliphatic  series.  When  treated  with  potassium  cyanide  benzaldehyde 
polymerizes,  or  better,  condenses  as  follows: 

C6H5— CHO+HCO— C6H6    >    C6H5— CH(OH)— CO— C6H5 

Benzaldehyde  Benzoin 

The  compound  formed  is  a  mixed  aromatic  alcohol  and  ketone,  i.e., 
(hydroxy-methyl-phenyl)  phenyl  ketone,  and  is  known  as  benzoin. 
This  compound  should  properly  be  considered  in  the  class  of  hydroxy 
ketones,  which  we  shall  take  up  a  little  later,  but,  because  of  its 
relation  to  benzaldehyde,  it  may  also  be  mentioned  here. 

Oxidation  of  Ketones. — The  aromatic  ketones  in  which  both  an 
aromatic  and  aliphatic  group  are  present  undergo  an  important  reaction 
when  oxidized.  Ordinarily  ketones  can  not  be  oxidized  without 
breaking  down,  because  the  carbon  group  containing  the  carbonyl 
oxygen  has  no  remaining  hydrogen  atom  united  to  it.  In  the  case  of  an 
aromatic-aliphatic  ketone,  e.g.,  C6H5 — CO — CH3,  the  oxidation  con- 
sists in  the  conversion  of  the  alkyl  radical  into  carboxyl  as  follows: 

C6H5— CO—  CH3+O    >    C6H5— CO— COOH 

Phenyl  methyl  ketone  Benzoyl  formic  acid 

The  compound  so  formed  is  a  mixed  ketone  acid  and  as  such  will  be 
referred  to  again. 

Oximes  and  Hydrazones. — The  characteristic  aldehyde  and  ketone 
reactions  with  hydroxyl  amine  and  phenyl  hydrazine,  depending  upon 
the  carbonyl  group,  =C  =  O,  take  place  with  the  aromatic  aldehydes 
and  ketones  just  as  they  do  with  the  aliphatic  and  yield  oximes  and 
hydrazones,  the  former  being  of  especial  importance. 

C6H5— CH=  (0+H2)N— NH— C6H5 »C6H5— CH  =  N— NH— C6H5 

Benzaldehyde  Phenyl  Phenyl  hydrazone  of 

hydrazine  benzaldehyde 

C6H5     CH=(0+H2)— N— OH       — >     C6H5— CH  =  N— OH 

Benzaldehyde  Hydroxyl  Benzaldoxime 

amine 

Isomerism  of  Benzaldoxime. — Benzaldoxime,  the  product  of  the 
last  reaction,  exhibits  a  very  interesting  case  of  stereo-isomerism.  It 
exists  in  two  forms  which  under  certain  conditions  are  readily  trans- 


652  ORGANIC  CHEMISTRY 

formed  into  each  other.  This  isomerism  is  stereo-isomerism  of  the 
nitrogen  atom  of  the  same  nature  as  was  found  in  the  case  of  the  diazo 
compounds  (p.  592).  The  formulas  expressing  the  isomeric  forms  are  as 
follows  : 

CeHs  —  C  —  H  CgHs  —  C—  "-H 


N—  OH  HO—  N 

Benz-syn-aldoxime  Benz'-anti-aldoxime 

m.p.  125°  m.p.  35° 

The  indication  that  the  syn  formula  applies  to  that  benzaldoxime 
which  melts  at  125°  and  not  to  the  one  which  melts  at  35°,  is  that  the 
former  readily  loses  water  and  is  converted  into  phenyl  cyanide  or 
benzoic  nitrile.  This  will  be  clearly  seen  as  follows: 

C6H5—  C  (H)  -  H2O          C6H5—  C  =  N 

--  >  Phenyl  cyanide 

N—  (OH) 

Benz-syn-aldoxime 

The  anil  form,  with  the  hydroxyl  and  the  hydrogen  on  opposite  sides, 
would  not  thus  easily  lose  water,  and  in  fact  it  does  not. 

The  naming  of  the  isomeric  aldoximes  follows  the  same  plan  as  in  the 
case  of  the  diazo  compounds  (p.  592),  the  prefixes  syn  and  anti  being 
used.  The  prefix  syn  means  that  the  hydroxyl  group  is  on  the  same 
side  of  the  doubly  linked  nitrogen  and  carbon  atoms  as  some  other 
group  while  anti  indicates  that  the  two  are  on  opposite  sides.  In  the 
diazo  compounds  the  phenyl  or  other  benzene  group  is  the  only  other 
group  present  and  the  terms  syn  and  anti  refer  to  the  relation  of  the 
hydroxyl  group  to  this  benzene  group. 

C6H5—  N  C6H5—  N 

II  II 

KO  N  N—  OK 

Potassium  syn-benzene  Potassium  anti-benzene 

diazotate  diazotate 

In  the  oximes  of  the  aromatic  aldehydes  and  ketones,  however,  two 
other  groups  are  present  and  the  names  must  indicate  to  which  of  these 
groups  the  syn  or  anti  relationship  of  the  hydroxyl  group  applies. 

C6H5—  C—  H  C6H5—  C—  H 

II  II 

N—  OH  HO—  N 

Benz-syn-aldoxime  Benz-anti-aldoxime 


AROMATIC   ALDEHYDES    AND    KETONES  653 

The  prefix  is  placed  immediately  before  the  name  of  the  group  con- 
cerned, i.e.,  syn-aldoxime  means  that  the  aldehyde  hydrogen  atom  is 
syn  to  the  hydroxyl  group  and  anti-aldoxime,  that  the  aldehyde  group  is 
anti  to  the  hydroxyl  group.  If  the  prefixes  referred  to  the  benzene 
group  the  names  would  be  reversed  and  benz-syn-aldoxime  would 
be  anti-benzaldoxime  and  benz-anti-aldoxime  would  be  syn-benzal- 
doxime.  These  last  names,  however,  are  not  used. 

Isomerism  of  Ketoximes.  —  In  the  case  of  aromatic  aldehydes  they 
all  yield  these  stereo-isomeric  oximes.  With  the  aromatic  ketones  the 
condition  is  different  and  some  yield  stereo-isomers  and  some  do  not. 
With  symmetrical  aromatic  ketones  in  which  the  two  radicals  are  alike, 
such  as  di-phenyl  ketone,  C6H5  —  CO  —  C6H,5  no  different  space  rela- 
tion of  the  hydroxyl  group  is  possible  as  the  two  forms  will  be  identical. 
When,'  however,  the  ketone  is  unsymmetrical,  i.e.,  the  two  radicals  are 
unlike,  as  in  mixed  aromatic-aliphatic  ketones  such  as  phenyl  methyl 
ketone,  C6H5  —  CO  —  CH3,  or  in  unsymmetrical  di-aryl  ketones  such  as 
phenyl  tolyl  ketone,  C6H5  —  CO  —  C6H4  —  CH3,-  then  the  two  stereo  forms 
are  possible  though  both  forms  are  not  known  in  all  cases. 

s  —  C  —  CH3  CeH  5  —  C  —  CH3 


HO—  N  N—  OH 

syn-Phenyl  methyl  ketoxime  anti-Phenyl  methyl  ketoxime 

(only  one  kndwn) 
4  —  CH3  CeHs  —  C  —  CeH4  —  CH3 


HO—  N  N—  OH 

syn-Phenyl  tolyl  ketoxime  anti-Phenyl  tolyl  ketoxime 

(both  known) 

As  just  stated  the  two  possible  stereo-isomers  are  not  always  known. 
The  stability  and  possible  isolation  of  the  two  forms  seems  to  be  con- 
nected with  the  linkage  of  benzene  rings  or  alkyl  radicals  to  the  carbo- 
oxime  group, 

—  C  —  .     In  aldehydes,  if  this  group  is  linked  to  an  alkyl  radical, 

HO—  N 

as  in  acetaldoxime,  CH3  —  C  —  H,  or  in  phenyl  acet  aldoxime, 

HO—  N 


654  ORGANIC  CHEMISTRY 

C6H5 — CH2 — C — H,  only  one  form  is  known.     Similarly  in  the  ket- 

HO— N 

oximes  if  this  carbo-oxime  group  has  one  alkyl  radical  linked  to  it  only 
one  form  is  known,  as  in  phenyl  methyl  ketoxime,  C6H5 — C — CH3,  (see 

II 
HO— N 

above).  On  the  other  hand  unsymmetrical  di-aryl  ketoximes  in  which 
two  benzene  rings  are  linked  to  the  carbo-oxime  group  are  known  in  the 
two  forms  as  in  phenyl  tolyl  ketoxime,  C6H5 — C — C6H4 — CH3  or  in 

II 
HO— N(— OH) 

phenyl  chlor-phenyl  ketoxime,  C6H5 — C — C6H4C1. 

II 
HO— N(— OH) 

The  fact  that  only  one  form  is  known,  when  the  two  are  possible,  may 
be  due  to  extreme  instability;  one  form  readily  changing  over  to  the 
other,  so  that  only  one  is  isolated.  That  the  known  compound,  in 
those  cases  where  only  one  has  ever  been  isolated,  is,  in  fact  one  of  these 
stereo  forms,  probably  the  syn  form,  is  indicated  by  the  decomposition 
products  and  by  a  study  of  a  transformation  known  as  the  Beckmann 
rearrangement. 

Beckmann  Rearrangement. — When  phenyl  methyl  ketoxime,  aceto 
phenoxime,  is  treated  with  acid  chlorides  or  phosphorus  penta-chloride, 
it  is  converted  into  acet  anilide.     The  steps  in  the  reaction  are  as 
follows: 
C6HB— C— CH3  HO— C— CH3 

HO— N  C6H5— N 

Aceto  phenoxime 

O  =  C— CH3  or  CH3— CO— NH— C6H5 

C6H5 — NH        Acetanilide 
A.  ALDEHYDES 
Benzaldehyde,  C6H6— CHO 

Amygdalin. — Benzaldehyde,  the  simplest  of  the  aromatic  aldehydes, 
occurs  in  nature  as  a  constituent  part  of  the  glucoside  amygdalin,  in 


AROMATIC   ALDEHYDES    AND    KETONES  655 

bitter  almonds,  in  the  kernels  of  peach  stones  and  in  some  other  plants. 
The  glucoside  consists  of  benzaldehyde,  glucose  and  hydrocyanic  acid 
in  combination.  "When  this  undergoes  hydrolysis  these  three  constitu- 
ents are  obtained  as  the  products.  In  almonds  there  is  also  present  an 
enzyme  known  as  emulsin  which  possesses  the  property  of  effecting 
this  hydrolysis.  Therefore  when  bitter  almonds  are  ground  and  mixed 
with  cold  water,  enzymatic  hydrolysis  of  the  glucoside  occurs  and  one 
of  the  products  is  benzaldehyde.  Hence  the  aldehyde  is  commonly 
known  as  oil  of  bitter  almonds.  The  reaction  which  takes  place  in 
the  hydrolysis  of  amygdalin  is  as  follows : 

C20H27NOii  +  2H20    >     C6H5— CHO  +  2C6H12O6  +  HCN 

Amygdalin  Benzaldehyde  Glucose  Hydrogen 

cyanide 

Benzaldehyde  is  a  colorless  liquid  when  pure,  m.p.  —13.5°,  b.p. 
1 80°.  It  has  a  strong  odor  of  the  natural  oil  of  bitter  almonds  and  is 
used  as  a  flavoring  substance  and  in  perfumery.  Because  of  its  easy 
preparation  and  common  occurrence  it  has  been  thoroughly  studied 
and  the  reactions  which  it  undergoes  have  been  well  established.  It 
will  be  recalled  that  one  of  the  classic  joint  researches  of  Liebig  and 
Wohler,  and  one  which  did  much  for  the  establishment  of  the  radical 
theory,  was:  "Concerning  The  Radical  of  Benzole  Acid."  It  was 
their  study  of  oil  of  bitter  almonds  which  led  them  to  this  investigation 
published  in  1832  (p.  14).  The  aldehyde  is  easily  oxidized,  even  in  the 
air,  to  benozic  acid,  hence  its  name  benzole  aldehyde  or  benzaldehyde. 
This  oxidation  also  occurs  with  the  simultaneous  reduction  to 
benzyl  alcohol  so  that  when  it  is  treated  with  strong  potassium  hydrox- 
ide it  is  converted  partly  into  one  compound  and  partly  into  the  other. 
That  is,  two  molecules  act  together,  one  being  reduced  or  oxidized  at 
the  expense  of  the  other. 

oxidation 

C6H5— CHO  -^      C6H5— COOH 

reduc- 

C6H5— CH2— OH    <—        C6H5— CHO 

Benzyl  f-  Benzaldehyde 

alcohol  tlon  (2-mol.) 

In  its  general  reactions  it  is  like  all  aldehydes.  It  is  an  important 
reagent  in  all  cases  where  an  aldehyde  is  needed  and  in  the  manufacture 
of  certain  dyes,  e.g.,  malachite  green  (p.  747). 


656  ORGANIC  CHEMISTRY 

Higher  Aromatic  Aldehydes 

Cuminic  Aldehyde. — Only  two  of  the  higher  aldehydes  are  of  suffi- 
cient importance  to  require  mention,  viz.,  cuminic  aldehyde  and 
cinnamic  aldehyde.  The  first  is  the  aldehyde  of  iso-propyl  benzene 
with  the  aldehyde  group  in  the  para  position. 

/CH(CH3)2     (i) 
CeH/u 

XCHO  (4) 

Cuminic  aldehyde 

It  is  known  as  cuminic  aldehyde  because  of  its  occurrence  in  Roman 
oil  of  cumin.  It  oxidizes  to  an  aromatic  acid  known  as  cuminic  acid 
which  is  para  iso-propyl  benzole  acid.  On  further  oxidation  the  ali- 
phatic side  chain  is  likewise  oxidized  to  carboxyl  and  a  di-basic  acid, 
terrephthalic  acid,  results.  This  acid  is  obtained  by  the  complete  oxi- 
dation of  para-xylene  and  hence  is  a  para  compound.  This  establishes 
cuminic  aldehyde  as  a  para  compound  also. 

/CH(CH3)2  (i)  /CH(CH3)2(i)  XX)OH  (i) 

CeH4,  >  CeH4v  >    CeH^v 

XCHO  (4)  XCOOH       (4)  XCOOH  (4) 

Cuminic  aldehyde  Cuminic  acid  Terre-phthalic  acid 

Cinnamic  Aldehyde. — The  other  aromatic  aldehyde  which  we  shall 
mention  is  cinnamic  aldehyde.  It  contains  the  aldehyde  group  in 
the  side  chain  and  not  in  the  benzene  ring,  and  is  thus  an  aliphatic 
aldehyde  substitution  product  of  benzene.  The  aliphatic  side  chain 
is  also  an  unsaturated  chain.  Its  formula  is  C6H6 — CH=CH — CHO, 
and  it  may  be  considered  as  beta-phenyl  acrylic  aldehyde.  As  an 
aldehyde  it  yields  by  oxidation  an  acid,  viz.,  beta-phenyl  acrylic  acid 
or,  as  it  is  commonly  known,  cinnamic  acid.  The  aldehyde  is  found  in 
oil  of  cinnamon  obtained  from  cinnamon  bark,  hence  its  name  and  the 
name  of  the  acid.  The  most  important  synthesis  is  by  the  condensation 
of  benzaldehyde  and  acetaldehyde,  as  follows : 

C6H5— CH(O+H2)CH— CHO    >     C6H5— CH=CH— CHO 

Benzaldehyde  Acetaldehyde  Cinnamic  aldehyde 

Cinnamic  aldehyde  reacts  as  benzaldehyde  does  and  is  important  as  a 
synthetic  reagent  in  the  same  classes  of  reactions. 


AROMATIC   ALDEHYDES    AND    KETONES  657 

B.  KETONES 
Aceto  Phenone,  C6H5— CO— CH3,  Phenyl  Methyl  Ketone 

Only  two  individual  ketones  will  be  mentioned  in  detail  and  they 
have  already  been  repeatedly  referred  to  in  the  preceding  discussion 
of  general  facts.  They  are, 

C6H5 — CO — CH3,  Phenyl  methyl  ketone  or  Aceto  phenone. 
and          C6H5— CO — C6H5,  Di-phenyl  ketone  or  Benzo  phenone. 

Aceto  phenone  is  the  simplest  of  the  aromatic  ketones  related  to 
secondary  aromatic  alcohols.  It  is  a  crystalline  substance;  m.p. 
20.5°,  b.p.  202°.  It  possesses  a  soporific  or  hypnotic  effect  on  account 
of  which  it  is  also  known  as  hypnone.  Its  reactions  are  those  already 
considered.  The  oxime  produced  by  the  action  of  hydroxyl  amine 
would  seem  to  be  possible  of  existence  in  two  stereo-isomeric  forms  like 
the  benzaldoximes  as  the  two  radicals  joined  to  the  carbo-oxime  group 
are  different.  In  fact  only  one  oxime  is  known  as  has  been  explained. 

C6H5— C  — CH3    syn-Phenyl  methyl  ketoxime 

II  . 

HO — N  (anti-Aceto  phenoxime) 

The  proofs  that  the  known  form  is  the  syn  compound  are  that  it 
does  not  break  up  and  yield  phenyl  cyanide  and  that  it  yields  acet 
anilide  by  the  Beckmann  rearrangement  which  has  just  been  discussed 
(P-  654). 

Benzo  Phenone,  C8H6— CO— C6H5,  Di-phenyl  Ketone 

Benzo  phenone  is  a  solid  which  is  di-morphous,  i.e.,  it  exists  in  two 
forms  which  are  not  isomeric  as  they  possess  the  same  formula  in  every 
respect.  One  form  is  a  solid,  m.p.  26°,  while  the  other  is  a  solid,  m.p. 
46°.  On  reduction  with  zinc  dust  benzo  phenone  yields  first  the  corre- 
sponding secondary  alcohol,  C6H5 — CH(OH)— C6H5,  and  then  the 
hydrocarbon  di-phenyl  methane,  C6H5 — CH2 — C6H5. 

C6H5— CO— C6H6 >C6H5— CH(OH)— C6H5— »C6H5— CH2— C6H5 

Benzo  phenone  Di-phenyl  methane 

This  hydrocarbon,  di-phenyl  methane,  is  a  member  of  another  series 
which  will  be  considered  later  and,  strictly  speaking,  benzo  phenone  does 
not  belong  to  the  group  of  aromatic  ketones  which  we  have  been 
studying.  Because  of  its  close  analogy  to  the  other  aromatic  ketones 

42 


658  ORGANIC  CHEMISTRY 

it  seems  best,  however,  to  take  it  up  at  this  time.     Benzo  phenone 
being  symmetrical  in  constitution  yields  only  one  oxime, 


N— OH 

This  oxime,  however,  undergoes  the  Beckmann  rearrangement  and 
yields  benzanilide  just  as  aceto  phen-oxime  yields  acet  anilide. 

C^HB — C — CeHs  CeHs — C — OH  C&H.b — C  =  O 

II  II  I 

N— OH  N— C6H6  NHC6H6 

Benzo  phenone  oxime  ,  Benzanilide 

SUBSTITUTED  ALDEHYDES  AND  KETONES 
HYDROXY  ALDEHYDES  AND  HYDROXY  KETONES 

Phenol  Aldehydes  and  Ketones. — The  most  important  substitution 
products  of  aromatic  aldehydes  and  ketones  are  those  containing  the 
hydroxyl  group.  Analogous  to  the  phenol  alcohols  we  have  the  phenol 
aldehydes  and  phenol  ketones  which  are  ring  hydroxy  substitution  prod- 
ucts of  the  aromatic  aldehydes  and  ketones. 

CH2OH 
C6H5— CH2OH  C6H/ 

Alcohol  OH 

Phenol  alcohol 

OH 
CgHs — CHO  CgH4K 

Aldehyde  CHO 

Phenol  aldehyde 

OH 
C6H6— CO— C6H6  C6H/ 

Ketone  V**A      r1  TT 

CO — C6H5 

Phenol  ketone 

Some  members  of  this  class  of  compounds  and  especially  some  of  their 
ether  derivatives  are  very  valuable  natural  products. 

/OK 
Hydroxy  Benzaldehydes, 


PHENOL    ALDEHYDES  659 

Reimer-Tiemann  Reaction.  —  Both  the  ortho-  and  para-hydroxy 
benzaldehydes  are  important.  They  may  both  be  synthesized  by 
what  is  known  as  the  Reimer-Tiemann  reaction.  This  consists  of  the 
interaction  between  a  salt  of  a  phenol  and  chloroform  in  the  presence  of 
an  excess  of  alkali.  The  result  is  the  introduction  of  the  aldehyde 
group,  (  —  CHO),  into  the  benzene  ring  of  the  phenol  as  follows: 


C6H5—  OK    +    CHC13  +  3KOH       -»     C6H4<  +  3KC1 

ph°?nola"em  Chloroform  \CHO     +  ^Q 


Hydroxy  benzaldehyde 
(ortho  and  para) 

The  reaction  probably  takes  place  by  the  following  steps: 
OK  X)K 


+  2K)—  OH  -     * 
(H  +  Cl)—  CHC12  CH(C12 

OK  OK 

C6H4  0(H)       l£!?     C6H4< 

XCHO 
(OH 

The  reaction  is  a  general  one  for  phenols  both  mono-  and  poly-,  and  for 
the  ethers  of  poly-phenols.  It  results  always  in  a  mixture  of  the  ortho 
and  para  compounds.  In  the  preparation  of  hydroxy  benzaldehyde 
the  two  may  be  easily  separated  as  the  ortho  compound  is  volatile  with 
steam,  while  the  para  compound  is  not. 

Salicylic  Aldehyde.  —  The  ortho-hydroxy  benzaldehyde  is  also 
known  as  salicylic  aldehyde  because  on  oxidation  it  yields  salicylic 
acid,  ortho-hydroxy  benzoic  acid.  It  may  also  be  made  by  oxidizing 
ortho-hydroxy  benzyl  alcohol,  salicylic  alcohol  (p.  646),  or  by  oxidizing 
the  glucoside  salicin  from  which  the  alcohol  is  obtained  on  hydrolysis. 
It  occurs  naturally  in  the  oil  of  the  flowers,  leaves  and  stems  of  certain 
spiraea  plants.  It  is  an  oil  with  a  characteristic  odor.  At  —  20°  it 
solidifies  to  large  crystals  and  it  boils  at  196.5°.  It  is  slightly  soluble 
in  water  and  gives  a  violet  color  with  ferric  chloride.  It  reduces 
Fehling's  solution  and  forms  a  crystalline  addition  compound  with 
sodium  acid  sulphite  like  aldehydes  in  general.  It  yields  an  oxime  and 
a  hydrazone,  the  former  known  in  one  stereo  form,  the  latter  in  two. 


660  ORGANIC  CHEMISTRY 

(2)  d) 

HO— C6H4— C— H 
HO— N 

ortho-Hydroxy  benz 
anti-aldoxime 

HO— C6H4— C— H  HO— C6H4— C— H 

II  II 

C6H5— NH— N  N— NH— C6H5 

ortho-Hydroxy  benz  ortho-Hydroxy  benz 

anti-aldehydrazone  syn-aldehydrazone 

para-Hydroxy  Benzaldehyde. — Besides  being  formed  together  with 
the  ortho  compound  by  the  Reimer-Tiemann  reaction  the  para 
hydroxy  benzaldehyde  may  be  synthesized  from  phenol  by  a  modifi- 
cation of  the  Gattermann-Koch  reaction  (p..  649),  for  introducing 
the  aldehyde  group  into  a  benzene  ring.  In  this  synthesis  hydrogen 
cyanide  and  hydrochloric  acid,  together  with  aluminium  chloride,  are 
used.  The  first  two  react  similarly  to  carbon  monoxide  and  hydro- 
chloride  acid  (p.  649)  and  give  the  chloride  of  imino  formic  acid. 

H— CN  +  HC1 >  Cl— C— H 

NH 

Imino  formic  acid  chloride 

In  the  presence  of  aluminium  chloride  this  compound  reacts  with  phenol 
yielding  an  ald-imide  which  with  water  gives  the  hydroxy  aldehyde. 

/OH 
4\(H  +  Cl)— CH  =  NH 

Phenol 

/OH  /OH 

C,H4<  +H2)0         >        C6H4< 

\CH=(NH  \CHO 

para-Hydroxy 
benzaldehyde 

The  advantage  of  this  synthesis  is  that  the  para  compound  only  is 
formed  and  that  phenol  ethers  undergo  the  reaction  also.  The  para- 
hydroxy  benzaldehyde  is  not  volatile  with  steam,  is  quite  soluble  in 


PHENOL   ALDEHYDES  66 1 

water  and  gives  only  a  slight  violet  color  with  ferric  chloride.  It  forms 
an  addition  product  with  sodium  acid  sulphite  and  an  oxime  and  hydra- 
zones  with  hydroxyl  amine  and  phenyl  hydrazine. 

Ethers.    Essential  Oils 

The  ether  derivatives  of  the  phenol  aldehydes  like  the  ether  deriva- 
tives of  the  phenols  themselves  are  important  as  constituents  of  essen- 
tial oils  present  in  many  plants. 

Anis  Aldehyde. — The  simplest  essential  oil  constituent  of  this 
group  is  one  found  in  anis  seed  oil  and  known  as  anis  aldehyde. 

/OCH3 
It  is  the  methyl  ether  of  para-hydroxy  benzaldehyde,  C6H4< 

\CHO 

It  is  a  liquid,  ni.p.  —  4°,  b.p.  245°,  with  a  pleasant  odor  of  white  thorne 
flowers  and  is  used  in  perfumes.  It  is  interesting  that  while  hydroxy 
benzaldehyde  itself  yields  only  one  form  of  oxime  the  anis  aldehyde 
yields  the  two  stereo-isomeric  forms.  This  is  attributed  to  the  influence 
of  the  free  hydroxyl  group  in  preventing  the  formation  of  isomers.  In 
the  anis  aldehyde  the  hydroxyl  group  is  converted  into  methoxy  and 
the  isomers  are  obtained. 

Protocatechuic  Aldehyde. — A  di-phenol  aldehyde,  viz.,  the  3-4- 
di-hydroxy  benzaldehyde,  is  known  as protocatechuic  aldehyde  because 
it  yields  protocatechuic  acid  on  oxidation. 

CHO 


OH 


OH 

Protocatechuic  aldehyde 

It  may  be  synthesized  by  the  Reimer-Tiemann  or  Gattermann-Koch 
reactions  from  pyrocatechinol,  i-2-di-hydroxy  benzene. 

Vanillin. — Two  very  important  essential  oil  constituents  are  ether 
derivatives.  One  of  these  is  vanillin,  the  chief  constituent  of  vanilla 
beans  from  which  vanilla  extract  is  made,  and  the  other  is  heliotropin, 
also  known  as  piperonal,  which  has  the  odor  of  heliotrope  flowers.  Van- 
illin is  the  mono-methyl  ether  of  protocatechuic  aldehyde,  the  methoxy 


662 


OEGANIC  CHEMISTRY 


group  being  in  the  meta  position  to  the  aldehyde  group.     Heliotropin 
is  the  methylene  di-ether  of  the  same  aldehyde.     The  formulas  are, 


CHO 


CHO 


OCIL 


OH 

Vanillin 

4-Hydroxy  3-methoxy 
benzaldehyde 


CH2 

Heliotropin  (Piperonal) 

3-4-Methylene  di-oxy 

benzaldehyde 


Just  as  protocatechuic  aldehyde  may  be  synthesized  by  the  Reimer- 
Tiemann  or  Gattermann-Koch  reactions  from  the  -di-phenol  pyro- 
catechinol,  so  vanillin  may  be  made  by  the  same  reactions  from  the 
mono-methyl  ether  of  pyrocatechinol,  i.e.,  guaiacol  (p.  621). 


CHO 


(CHC13  +  KOH) 
OCH3      (HCN  +  HC1  +  Aids) 


Guaiacol 


Vanillin 


Heliotropin  may  be  prepared  from  protocatechuic  aldehyde  by  the 
action  of  methylene  iodide,  CH2I2,  the  yield,  however,  being  small. 


CHO 


CHO 


0(H 


~   I2) ==  CH2 

Methylene  iodide 

Di-iodo  methane 


o 

(H 

Protocatechuic 
aldehyde 


TT  r  CH2 
Hehotropin 


Relation  to  Eugenole,  etc. — By  far  the  most  important  syntheses 
of  these  important  essential  oil  constituents  are  by  the  oxidation  of  the 
corresponding  ethers  of  di-hydroxyl  derivatives  of  benzene  homologues 


PHENOL   ALDEHYDES 


663 


which  contain  an  unsaturated  side  chain.  All  of  these  compounds  are 
important  essential  oil  constituents  and  the  syntheses  referred  to  have 
been  the  means  of  showing  the  relationship  between  them.  We  have 
previously  discussed  the  methyl  and  methylene  ethers  of  the  mono- 
and  di-phenols  with  unsaturated  side  chain  (p.  623).  Their  formulas 
may  be  repeated  as  follows: 


(4)  d) 

HO—  C6H4—  CH2—  CH  =  CH 

Chavicol 

(4)  (i) 

HO—  C6H4—  CH  =  CH—  CH3 


Anol 


(4)  (i) 

CH3O— C6H4— CH2— CH  =  CH2 

Estragole 

(4)  (i) 

CHsO— C6H4— CH  =  CH— CH3 


Anethole 


(4) 


y 
CHSC/ 

(3) 

Eugenole 


(i) 
s  —  CH2  —  CH  =  CH2 


(4) 


HO  (i) 

)C6H3— CH  =  CH— CH3 
CH3<y 


(3) 

Iso-eugenole 


(4) 


H°\ 


(3)     CH3(/ 

Coniferyl  alcohol 


(4) 


\/ 
(3) 

Safrole 


(i) 

,— CH2— CH  =  CH2 


C6H3— CH  =  CH— CH2OH  (i) 

hoi 

(4) 
/°\  (I) 

/  Xp    TT  /"«TT  _   /-ITT          f^TT 

2\  yU6±l3  Uil  ~   UJtl U±13 

X0/ 

(3) 

Iso-safrole 

It  will  be  recalled  that  the  difference  between  eugenole  and  safrole  on 
the  one  hand  and  the  corresponding  iso  compounds,  iso-eugenole  and 
iso-safrole,  on  the  other  is,  that  in  the  latter  and  also  in  coniferyl 
alcohol,  anol  and  anethole,  the  benzene  ring  is  in  the  alpha  or  i  position 
in  the  unsaturated  propene  or  propenol  chain.  When  such  an  unsatu- 
rated side  chain  compound  is  oxidized  the  chain  breaks  at  the  double 
bond  and  yields  the  aldehyde  of  the  benzene  compound. 

R— CH  =  CH— CH3  +  O    >    R— CHO 


The  following  reactions  and  relationships  have  thus  been  established, 
and  they  have  become  the  chief  synthetic  methods  used  in  the  prepara- 


664  ORGANIC  CHEMISTRY 

tion  of  these  valuable  compounds.  The  iso-compounds,  being  readily 
prepared  from  their  isomers,  either  set  of  compounds  may  thus  be  used 
as  a  source  of  the  preparation. 

(4)  (i)  (4)  (i) 

CH3O—  C6H4—  CH  =  CH—  CH3        -  >         CH3O—  C6H4—  CHO 

Anethole  Anis  aldehyde 

(4)     HO,  +  O  (4)   HO, 

V6H3—  CH  =  CH—  CH3(i)~  ">C6H3—  CHO  (i) 

(3)CHs(r  (3)  CHsO/ 

Iso-eugenole  Vanillin 

(4)  (4) 

HO,  (i)  +0  HO,  (i) 

"C6H3—  CH  =  CH—  CH2OH  ~V6H3  —CHO 


(3)  •  (3) 

Coniferyl  alcohol  Vanillin 

(4)  (4) 

/0\  (i)  +0  O,  (i) 

CH/      )C,Hr-  CH  =  CH—  CH3  CH 


(3)  (3) 

Iso-safrole  Heliotropin 

Vanillin  is  present  in  the  vanilla  bean  to  the  amount  of  about  2.0  per 
cent,  accumulating  as  white  crystalline  needles.  It  is  also  found  in 
smaller  amounts  in  several  other  plants  and  plant  resins  or  balsams, 
e.g.,  gum  benzoin,  Peru  balsam,  Tolu  balsam,  Orchideae  nigretella,  etc. 
It  crystallizes  in  white  needles,  m.p.  80°,  b.p.  285°,  soluble  in  90-1  oo 
parts  cold 'water  and  20  parts  of  hot.  It  possesses  the  characteristic 
odor  and  flavor  of  the  common  vanilla  extract.  It  is  now  prepared  in 
considerable  commercial  quantities  by  one  of  the  above  synthetic 
methods  mostly  from  eugenole  which  yields  first  iso-eugenole ;  or  from 
the  glucoside  coniferin,  which  yields  coniferyl  alcohol.  It  is  interesting 
that  the  synthetic  vanillin  can  be  used  in  all  cases  in  place  of  the  natural 
vanilla  extract  when  the  object  is  odor,  as  in  perfumes,  the  aroma  being 
similar  but  weaker.  When  it  is  used  as  a  flavor  the  synthetic  product 
can  only  partially  replace  the  natural.  This  is  due  to  the  fact  that  in  the 
synthetic  product  it  is  very  difficult  to  remove  all  traces  of  the  by-prod- 
ucts. Pure  vanillin  costs  about  $50  to  $60  per  pound.  A  water  solu- 
tion of  vanillin  acts  weakly  acid  and  is  colored  by  ferric  chloride  a  slight 


PHENOL   ALDEHYDES  665 

blue-  violet.  It  yields  characteristic  oximes  and  hydrazones.  When 
heated  with  hydrochloric  acid  it  hydrolyzes  to  protocatechuic  aldehyde, 
and  when  fused  with  potassium  hydroxide  it  yields  the  corresponding 
di-hydroxy  acid. 

Heliotropin,  Piperonal.—  Heliotropin  receives  its  other  name  of 
piperonal  from  its  relation  to  compounds  occurring  in  pepper.  In 
black  pepper,  Piperus  nigra,  there  is  present  an  alkaloid  known  as 
pipeline  (p.  888).  From  this  alkaloid  an  acid,  piperic  acid,  is,  obtained. 
This  acid  is  a  methylene  di-ether  containing  an  alpha  unsaturated  side 
chain  as  in  iso-eugenole,  etc.  On  oxidation  the  side  chain  breaks  at 
the  double  bond,  as  has  been  explained,  and  yields  an  aldehyde  which  is 
piperonal. 

(4) 
/°\  +0 

CH/         C«H3—  CH=CH—  CH  =  CH—  COOH  (i) 


(3) 

Piperic  acid 

(4) 


CH  C6H3—  CHO  (i) 


(3) 

Piperonal,  Heliotropin 

Heliotropin  is  prepared  commercially  by  the  synthesis  given  above 
from  safrole  through  iso-safrole.  It  is  used  in  perfumes  on  account  of 
its  very  pleasant  odor  of  heliotrope  flowers.  It  forms  crystals,  m.p. 
37°,  b.p.  263°.  By  boiling  with  water  it  hydrolyzes  and  yields  proto- 
catechuic aldehyde  just  as  vanillin  does.  It  also  yields  oximes  and 
hydrazones  which  are  characteristic. 

Alcohol-aldehydes  and  -ketones.  —  If  the  hydroxyl  group  in 
hydroxy  aldehydes  and  ketones  is  in  the  side  chain  instead  of  the  ring 
then  the  compounds  instead  of  being  mixed  phenol-aldehydes  will  be 
alcohol-aldehydes  or  -ketones,  e.g., 

C6H5—  CH(OH)—  CH(OH)—  CH(OH)—  CHO 

Phenyl  tetrose 

2-3-4-  Tri-hydroxy  4-phenyl  butyric  aldehyde 

C6H5—  CO—  CH2OH 

Hydroxy  aceto  phenone 


666 


ORGANIC  CHEMISTRY 


Such  compounds,  if  they  contain  more  than  two  hydroxyl  carbon  groups 
in  the  saturated  side  chain,  are  plainly  phenyl  derivatives  of  the  sugars 
as  in  the  first  formula  above. 

AMINO  KETONES 

Nitro  and  ammo  substituted  aromatic  aldehydes  and  ketones  are 
not  of  special  importance  except  in  two  cases  that  may  be  cited. 

ortho-Amino  Benzophenone. — Benzophenone  yields  an  ortho- 
nitro  substitution  product  with  the  nitro  group  substituted  in  one  of  the 
benzene  rings  in  the  position  ortho  to  the  carbonyl  group.  This  nitro 
compound  by  reduction,  like  all  nitro  compounds,  yields  the  correspond- 
ing amino  compound.  When  this  ortho-amino  benzophenone  is 
oxidized  two  hydrogens  are  lost,  one  from  the  amino  group  and  the 
other  from  the  benzene  ring  which  is  not  joined  to  nitrogen,  and  the  two 
groups  become  united.  This  results  in  a  compound  in  which  two  ben- 
zene rings  are  doubly  linked  to  each  other  on  one  hand  by  the  carbonyl 
group  of  the  original  benzophenone  and  on  the  other  by  the  imino 
group  as  follows: 


-2H 


ortho-Amino 
benzophenone 


667 


The  compound  formed  is  known  as  acridon. 

Michler's  Ketone. — A  similar  di-amino  compound  in  which  two 
amino  groups  are  substituted  in  benzophenone  in  the  para  position 
in  each  of  the  benzene  rings  yields  a  tetra-methyl  amino  product  which 
is  known  as  Michler's  ketone. 


H2N—  C6H4—  Ca-C6H4— NH2 

para -para -Di-amino 
benzophenone 


:6H4— N(CH3)2 


(CH3)2N— C6H4- 

Tetra-methyl  para-para-di-amino 
benzophenone 
Michler's  ketone 


Auramine. — When  this  Michler's  ketone  is  treated  with  ammonium 
chloride  water  is  lost  and  a  compound  is  formed  of  the  constitution 
shown  in  the  following  reaction: 


(CH3)2  =  N- 


— C— 

(O) 


-N=(CH3)2 


(H2) 
Cl— NH2 

Michler's  ketone + Ammonium  chloride 


(CH3)2  =  N  = 
Cl 


N-/  /=C     \  V-N  =  (CH3)2 


NIL 


Auramine 


668  ORGANIC  CHEMISTRY 

In  this  compound  one  of  the  amino  nitrogens  becomes  penta-valent  as 
in  ammonium  salts  while  the  other  remains  tri-valent.  The  benzene 
ring  to  which  the  penta-valent  nitrogen  is  linked  takes  on  the  quinoid 
structure  as  in  quinone,  while  the  other  benzene  ring  retains  its  normal 
ring  structure.  The  compound  which  is  formed  is  known  as  auramine, 
and  is  the  mother  substance  of  important  dyes.  As  will  be  mentioned, 
in  connection  with  dyes,  the  presence  of  a  quinoid  group  is  associated 
with  the  dye  character  of  compounds. 


IX.  AROMATIC  ACIDS 

Character  and  Types. — Aromatic  acids  bear  exactly  the  same  rela- 
tionship to  aromatic  primary  alcohols  and  aldehydes  that  the  aliphatic 
acids  do  to  the  aliphatic  primary  alcohols  and  aldehydes,  i.e.,  the  acids 
are  the  final  oxidation  products  of  the  other  two  groups.  In  the  alipha- 
tic series  we  showed  how  the  alcohols  may  be  considered  as  the  first 
oxidation  products  of  the  hydrocarbons.  The  entire  series  of  oxidation 
relationships  being  illustrated  as  follows: 

CH3— CH3    JL2     CH3— CH2OH     +  °t 

Ethane  Ethanol 

Hydrocarbon  Alcohol 

CH3— CHO     JL2      CH3— COOH 

Ethanal  Ethanoic  acid 

Aldehyde  Acid 

Methyl  to  Carboxyl. — In  other  words  the  acid  group  — COOH' 
carboxyl,  is  the  complete  oxidation  product  of  the  methyl  group.  In 
the  aliphatic  series  the  first  step;  methyl  group  to  primary  alcohol 

group,    ( — CH3) >( — CH2OH),  and  also   the  complete  oxidation, 

methyl  group  to  carboxyl  group,  ( — CH3) >( — COOH);  has  never 

been  accomplished  as  a  laboratory  process.  However,  the  other 
steps  have  been,  and  the  relationship  is  accepted  as  practically  es- 
tablished. The  acceptance  of  it  as  a  true  relationship  has  been  strength- 
ened by  the  fact  that  in  the  benzene  series  the  complete  oxidation  of 
methyl  to  carboxyl  is  an  easily  accomplished  and  common  operation. 
The  series  of  reactions  may  be  illustrated,  for  the  benzene  compounds, 
as  follows: 

C6H5— CH3     _JlS     C6H5~ CH2OH    _JI_S 

Toluene  Benzyl  alcohol 

C6H5— CHO    jt-S     C6H5— COOH 

Benz-aldehyde  Benzoic  acid 

Oxidation  of  Hydrocarbons. — In  this  case  also  the  first  step  does 
not  take  place,  though  the  reverse,  the  reduction  of  benzyl  alcohol  to 
toluene  is  easily  accomplished.  The  important  fact  now,  in  connection 

669 


670  ORGANIC  CHEMISTRY 

with  the  aromatic  acids,  is,  that  a  common  general  method  of  synthesiz- 
ing them  is  by  the  oxidation  of  a  methyl  group  to  carboxyl  and  for 
each  methyl  group  linked  to  a  benzene  ring  a  carboxyl  group  is  the 
final  oxidation  product.  In  this  way  we  may  obtain  not  only  mono- 
but  also  poly-carboxy  acids.  It  is  also  true,  that  not  only  a  single 
methyl  group  linked  to  a  benzene  ring,  but  any  poly-carbon  saturated 
side  chain,  will  yield  the  carboxyl  group  as  the  final  oxidation  product. 
These  relationships  may  be  illustrated  by  reactions  which  have  been 
previously  referred  to  (p.  486),  viz.,  that  toluene,  methyl  benzene, 
yields  benzole  acid,  carboxy  benzene;  and  mesitylene,  tri-methyl 
benzene,  yields  successively  a  mono-carboxy,  a  di-carboxy  and  a  tri- 
carboxy  acid. 

C6H6—  CH3  C6H5—  COOH 

Toluene  Benzoic  acid 

CH3  .COOK 

CH3         --  >          CeHs^—  CH3  -  > 

CH3  XCH3 

Mesitylene  Mesitylenic  acid 

.COOH 


CH3  COOH 

Uvitic  acid  Tri-mesitic  acid 

In  our  study  of  the  aromatic  aldehydes  we  have  also  stated  that  they 
are  synthesized  by  the  oxidation  of  benzene  hydrocarbons  containing 
an  unsaturated  side  chain,  in  which  the  double  bond  is  between  the 
first  and  second  carbons  from  the  benzene  ring.  The  aldehydes  then 
being  oxidizable  to  the  acids  gives  us  a  second  class  of  hydrocarbons 
from  which  the  acids  may  be  obtained  by  oxidation. 

C6H5—  CH  =  CH—  CH3    Jl2    C6H5—  CHO    jL2    C6H6—  COOH 

i-PhenylAi-propene  Benzaldehyde  Benzoic  acid 

Thus  we  see  that  no  matter  what  the  nature  of  the  side  chain  group  in  a 
benzene  hydrocarbon,  whether  a  single  methyl  group,  a  saturated 
poly-carbon  chain  or  an  unsaturated  poly-carbon  chain,  each  side  chain 
always  yields  the  carboxyl  group  as  the  final  product.  The  intermediate 
products,  however,  and  the  ease  with  which  the  oxidation  is  effected 
varies  with  the  character  of  the  side  chain  so  that  in  compounds  con- 
taining two  or  more  different  hydrocarbon  side  chains  one  will  be  oxid- 


AROMATIC   ACIDS 


671 


ized  more  easily  than  another.  In  general  we  may  say;  (a)  The  longer 
side  chain  is  always  oxidized  the  more  easily,  (b)  The  side  chain 

/      /c\ 

containing  a  tertiary  carbon  group,    —  CH<T       I,  is  always  more  easily 

\        ^c/ 

oxidized  than  a  single  methyl  group  or  a  chain  containing  only  primary 
or  secondary  carbon  groups,  (c)  With  saturated  side  chains  the  inter- 
mediate products  are  probably  alcohols,  the  hydroxyl  group  being 
formed  from  a  hydrogen  of  the  carbon  group  linked  to  the  ring,  this 
alcohol  group  then  oxidizing  to  the  carboxyl  group,  (d)  With  un- 
saturated  side  chains  the  intermediate  product  is  an  aldehyde  which 
then  oxidizes  to  the  acid. 

Halogen  Substitution  and  Oxidation.  —  In  -the  oxidation  of  these 
hydrocarbons  to  the  corresponding  acids  the  reaction  may  be  accom- 
plished with  a  variety  of  reagents.  Toluene,  for  example  may  be 
oxidized  to  benzoic  acid  by  means  of  dilute  nitric  acid  or  chromic  acid. 
In  the  case  of  ring  substituted  hydrocarbons  the  oxidation  is  even  more 
easily  effected  and  potassium  permanganate  may  be  used.  The  oxida- 
tion is  often  accomplished  more  easily  by  indirect  processes.  Chlorine 
may  be  first  substituted  in  the  side  chain  and  then  the  chlorine  product 
by  hydrolysis  yields  either  an  alcohol  or  an  aldehyde.  These  are  then 
oxidized,  often  by  means  of  the  chlorine  first  used  as  a  substituting 
agent,  yielding  finally  the  acid.  In  the  case  of  benzo  tri-chloride  the 
chlorine  substitution  product  yields  the  acid  directly  by  hydrolysis. 


C6H6-CH3 

Toluene 


C6H6-CH3 

Toluene 


C6H6-CH3 

Toluene 


C6H6-CH2C1 

Benzyl  chloride 

C6H5—  CH2OH 

Benzyl  alcohol 


C6H6-CHC12 

Benzal  chloride 

C6H5—  CHO 

Benzaldehyde 


C6H5-CC13 

Benzo  tri-chloride 


C6H5—  COOH 

Benzoic  acid 


C6H5—  COOH 

Benzoic  acid 


COpH 

Benzoic  acid 


Ring  Carboxyl.—  In  all  of  the  cases  cited  the  acid  resulting  is  a 
ring  carboxy  benzene  product  and  such  an  acid  will  always  result  from 


672  ORGANIC  CHEMISTRY 

the  oxidation  of  any  side  chain  or  from  the  chlorination  and  subsequent 
oxidation  of  a  single  carbon  side  chain,  i.e.,  methyl. 

Side-chain  Carboxyl. — If,  however,  the  side  chain  consists  of  more 
than  one  carbon  group  the  halogenation  and  subsequent  oxidation  will 
result  in  another  type  of  aromatic  acid  if  the  halogen  is  at  the  end  of  the 
chain  and  possible  of  yielding  a  primary  alcohol  or  an  aldehyde. 

C6H5— CH2— CH3        >         C6H5— CH2— CH2C1        > 

Phenyl  ethane  i-Chlor  2-phenyl 

ethane 

C6H5— CH2— CH2OH        >         C6H5— CH2— COOH 

i-Hydroxy  2-phenyl  Phenyl  acetic 

ethane  acid 

C6H5— CH  =  CH— CHa    >     C6H5— CH  =  CH— CH2C1    > 

i -Phenyl  i -Phenyl  3-chlor 

Ai-propene  Ai-propene 

C6H5— CH  =  CH— CH2OH  — *        C6H5— CH  =  CH— COOH 

i -Phenyl  3-hydroxy  Cinnamic  acid 

Ai-propene 

In  such  a  product  the  carboxyl  group  instead  of  being  in  the  ring  is  in 
the  side  chain  and  while  it  is  considered  as  an  aromatic  acid  it  is  really 
a  benzene  derivative  of  an  aliphatic  acid  and  has  the  character  and 
properties  of  such  an  acid,  its  synthesis  as  above  being  exactly  analo- 
gous to  the  general  method  of  synthesizing  aliphatic  acids.  Such 
acids  also  may  be  either  mono-carboxy  or  poly-carboxy  if  the  character 
of  the  side  chain  is  branched,  giving  more  than  one  end  carbon  group 
and  making  more  than  one  carboxyl  group  possible. 

Mixed  Ring  and  Side-chain  Carboxyl. — Still  a  third  type  of 
aromatic  acid  is  possible,  viz.,  one  in  which  both  of  the  preceding 
types  are  present,  i.e.,  one  or  more  carboxyl  groups  may  be  in  the  ring 
and  at  the  same  time  one  or  more  may  be  in  the  side  chain,  e.g., 

CH2— COOH  (i)  CH2— CH2— COOH  (i) 

COOH  (2)  \X)OH  (2) 

Iso-uvitic  acid  ortho-Carboxy  hydro- 

cinnamic  acid 

CH  =  CH— COOH  (i) 
COOH  (2) 

ortho-Carboxy  cinnamic 
acid 


AROMATIC   ACIDS  673 

We  can  readily  see  what  a  variety  of  acids  are  possible  in  the  benzene 
series.  Not  all  of  the  types  mentioned  have  individual  members  of 
sufficient  importance  to  be  taken  up  in  detail,  but  the  foregoing  discus- 
sion will  illustrate  the  scope  of  the  group.  For  the  sake  of  clearness 
we  may  summarize  the  classes  of  aromatic  acids  with  the  following 
examples. 

I.  Ring  Carboxy  Acids. 


mono-basic,  C6H5— COOH        C6H4< 

Benzoic  acid  NCOOH 

Toluic  acids 

COOH  .COOH 

poly-basic,     C6H4<^  C6H3\-COOH 

XCOOH  XCOOH 

Phthalic  acids  Tri-mesitic  acid 

II.  Side-chain  Carboxy  Acids. 

saturated,     C6H5— CH2— COOH 


Phenyl  acetic 
acid 


C6H5— CH(COOH)— CH2— COOH 

Phenyl  succinic  acid 


unsaturated,     C6H5— CH  =  CH— COOH 

Cinnamic  acid 

C6H5— C(COOH)  =  CH— COOH 

Phenyl  maleic  acid 

III.  Mixed  Ring  and  Side-chain  Carboxy  Acids. 

CH2— CH2— COOH 
saturated,       C6H4<\ 

XCOOH 

«  ortho-Carboxy  hydro - 

cinnamic  acid 

CH=CH— COOH 

unsaturated,  C6H4<^ 

XCOOH 

ortho-Carboxy 
cinnamic  acid 

Synthesis  of  Ring  Carboxy  Acids.— We  have  just  discussed  the 
synthesis  of  aromatic  acids  by  the  oxidation  of  benzene  hydrocarbons 
containing  a  side  chain.  As  would  be  expected  from  our  description 

43 


674  ORGANIC  CHEMISTRY 

of  the  different  types  of  these  acids  the  methods  of  synthesis  are  several. 
The  two  distinct  types,  viz.,  those  in  which  the  carboxyl  group  is  in 
the  ring  and  those  in  which  the  carboxyl  group  is  in  the  side  chain,  will 
naturally  be  formed  by  different  kinds  of  reactions;  the  former  by  those 
characteristic  in  general  of  benzene  compounds,  the  latter  by  those 
characteristic  of  aliphatic  compounds  and  which  are  used  in  synthesiz- 
ing aliphatic  acids. 

From  Hydrocarbons,  Friedel-Craft. — The  aromatic  hydrocarbons 
yield  ring  carboxy  acids  by  other  reactions  than  those  effecting  oxida- 
tion of  a  side  chain.  Carbon  dioxide  may  be  introduced  directly 
into  a  benzene  ring,  thus  converting  a  hydrogen  into. carboxyl.  This 
may  be  accomplished  in  the  presence  of  aluminium  chloride,  Friedel- 
Craft  reagent. 

C6H5— H  +  CO2(+A1C13)  — >        C6H5— COOH 

Benzene  Benzoic  acid 

The  intermediate  products  are  complex  compounds  containing  alumi- 
nium, but  the  end  product  is  the  acid  as  above.  The  same  result  is 
accomplished  if  carbonyl  chloride,  COC12,  is  used  instead  of  carbon 
dioxide,  the  first  formed  acid  chloride  being  hydrolyzed  to  the  acid. 

C6H5— (H  +  Cl)— CO— Cl         (  " 

Benzene 

C6H5— CO(C1  +  H)— OH  -->        C6H5— COOH 

Benzoyl  chloride  Benzoic  acid 

This  reaction  does  not  yield  good  results  because  the  acid  chloride 
reacts  with  the  hydrocarbon  forming  a  ketone. 

Gattermann  Synthesis. — Still  another  reaction  accomplishes  the 
same  purpose.  This  is  by  the  use  of  chlor  formamide,  Cl — CO — NH2, 
and  is  similar  to  the  reaction  with  carbonyl  chloride.  It  yields  first 
the  acid  amide  which  is  hydrolyzed  to  the  acid. 

C6H5— (H  +  Cl)— CO— NH2  -* 

Benzene  Chlor  formamide 

C6H6— CO(NH2+  H)— OH  *H>        C6H5— COOH 

Benzamide  Benzoic  acid 

This  is  known  as  the  Gattermann  synthesis  and  yields  better  results 
than  the  preceding  synthesis. 


AROMATIC   ACIDS  675 

From  Aryl  Halides.  Kekule  Synthesis. — Aromatic  halides  in  which 
the  halogen  is  in  the  ring  yield  ring  carboxy  acids  by  the  action  of 
carbon  dioxide  and  sodium. 

C6H5— Br  +  CO2  +  Na2  — >        C6H5— COONa  +  NaBr 

Brom  benzene  Benzole  acid 

(salt) 

The  reaction  is  known  as  the  Kekule  synthesis  and  is  analogous  to  the 
formation  of  aliphatic  acids  by  the  action  of  carbon  dioxide  on  sodium 
alkyls  (p.  132). 

CH3— Na  +  CO2        >        CH3— COONa 

Sodium  methyl  Acetic  acid  (salt) 

Wurtz  Synthesis. — The  introduction  of  carboxyl  in  place  of  a 
halogen  in  the  ring  may  also  be  effected  by  the  action  of  an  ester  of 
chlor  formic  acid  and  sodium. 

C6H5— (Br  +  Na)— (Na  +  Cl)— COOC2H5        > 

Brom  benzene  Ethyl  chlor  formate 

C6H5— COOC2H5  +  H2O  -^        C6H5— COOH 

Ethyl  benzoate  Benzoic  acid 

This  synthesis  was  first  carried  out  by  Wurtz  and  is  known  by  his 
name.  It  is  similar  to  the  like  synthesis  of  hydrocarbons  (p.  16). 

From  Sulphonic  Acids. — When  a  salt  of  a  sulphonic  acid  is  fused  with 
sodium  formate  the  sulphonic  acid  group  is  replaced  by  the  carboxyl 
group. 

C6H5— (SO2OK  +  H)— COONa    >    C6H5— COONa  +  KHSO3 

Benzene  sulphonic  Sodium  Benzoic  acid 

acid  (salt)  formate  (salt) 

This  is  similar  to  the  use  of  chlor  formic  acid  and  chloi  formamide  in  the 
preceding  syntheses.  The  method  was  first  used  by  Victor  Meyer. 
Sulphonic  acids  are  also  the  starting  point  for  the  synthesis  of  acids 
through  the  intermediate  acid  nitrile  as  described  next. 

From  Aryl  Cyanides  (Acid  Nitrites). — The  aromatic  cyanides  which 
were  simply  referred  to  as  substitution  products  (p.  521)  are,  of  course, 
like  the  aliphatic  cyanides,  nitriles  of  acids  which  they  yield  on 
hydrolysis. 

R— CN    +     2H2O        >        R— COOH  +  NH3 

Aryl  (or  alkyl)  Acid 

cyanide 
Acid  nitrile 

They  are  thus  a  general  source  for  the  synthesis  of  acids. 


676  ORGANIC  CHEMISTRY 

Nitriles  from  Sulphonic  Acids  or  Aryl  Halides. — Individual  acid 
nitriles  will  be  mentioned  at  various  times  whenever  they  are  used  in 
preparing  various  acids.  Several  reactions  may  be  employed  to  pre- 
pare the  nitriles  in  which  the  cyanogen  group  is  in  the  ring.  The  sim- 
plest method  is  from  sulphonic  acids  by  heating  with  potassium  cyanide. 

C6H5— (S02OK  +  K)— CN        > 

Benzene  sulphonic 
acid  (salt) 

K2SO3    +    C6H5— CN  +  2H2O  — >        C6H5— COOH 

Phenyl  cyanide  Benzoic  acid 

Benzoic  nitrile 

The.  synthesis  of  the  acid  from  the  nitrile  thus  becomes  in  reality 
a  synthesis  from  sulphonic  acids.  An  exactly  analogous  reaction  takes 
place  when  an  aryl  halide,  with  the  halogen  in  the  side  chain,  is  dis- 
tilled with  potassium  cyanide,  as  discussed  later  (p.  678). 

C6H5— CH2(C1  +  K)CN        >        C6H5— CH2— CN 

Benzyl  chloride  Phenyl  acetic  nitrile 

Nitriles  from  Iso-thio-cyanates. — The  nitriles  may  also  be  made 
from  iso-thio-cyanates  (p.  73).  When  these  are  heated  with  copper 
the  sulphur  is  eliminated  and  the  iso-cyanides  or  iso-nitriles  are  obtained 
and  these  iso-cyanides  are  transformed  into  the  cyanide  or  nitrile. 

C6H5— N  =  C  =  S  +  Cu        >        C6H5— NC        > 

Phenyl  iso-  Phenyl  iso -cyanide 

thio-cyanate  Iso-nitrile 

C6H5— CN        >        C6H5— COOH 

Phenyl  cyanide  Benzoic  acid 

Nitrile 

From  Phenol  Esters. — Another  method  of  preparing  nitriles  is  by 
the  action  of  potassium  cyanide  on  the  phosphoric  acid  esters  of  phenols. 

3C6H6— (OH  -f  (H)0)3  =  PO        > 

Phenol  Phosphoric 

acid 

(C6H5— 0)3^PO  +  3K)CN  -*        3C6H5— CN 

Phenyl  phosphate  Benzoic  nitrile 

From  Acid  Amides  and  Anilides. — In  the  aliphatic  series  the 
cyanides  are  formed  from  the  acid  amides  by  loss  of  water,  the  amides 
themselves  resulting  from  the  ammonium  salts  by  a  similar  loss  of  water. 

-H2O                                             -H2O 
CH3— CO(O)NH2(H2)       >       CH3— C(O)— N(H2) > 

Ammonium  acetate  Acet  amide 

+  2H20 
CH3— CN CH3— COOH  +  NH3 

Acetic  nitrile  Acetic  acid 


AROMATIC  ACIDS  677 

This  shows  the  relationship  of  these  compounds  to  each  other  as  was 
fully  discussed  in  Part  I  (p.  148). 

In  the  aromatic  series  the  direct  conversion  of  acid  amides  into 
acid  nitriles  does  not  take  place  readily;  but  the  acid  itself  is  made  from 
the  acid  amide  by  the  reverse  process  as  indicated  above,  viz.,  by  hydra- 
tion  to  the  ammonium  salt  of  the  acid,  which  then  yields  the  acid.  A 
related  method,  however,  is  used  for  preparing  acids  from  anilides  of 
formic  acid.  Aniline  being  an  ammonia  compound  yields  acid-amide- 
like  products  with  aliphatic  acids,  e.g.,  acet  anilide,  CH3 — CO — NH — 
C6H5  (p.  556).  Such  a  compound  can  not,  however,  lose  water  in  the 
same  way  as  the  acid  amide  in  the  above  reaction  for  the  ammonia 
residue  in  an  anilide  contains  only  one  hydrogen.  Nevertheless 
anilides  lose  water  but  in  a  different  way.  In  the  case  of  the  anilide 
of  formic  acid,  i.e.,  formanilide,  H — CO — NH — C6H5,  the  loss  of  water 
results  in  a  compound  in  which  the  carbon  and  nitrogen  remain  linked 
to  the  benzene  ring  and  an  iso-cyanide  or  iso-nitrile  is  formed.  The  iso- 
nitrile  is  readily  converted  into  the  nitrile  and  the  acid  may  then  be 
obtained  from  that. 

'  -  H2O 

(H)— C(0)— N(H)— C6H5  C6H6— NC  — > 

Formanilide  Phenyl  iso- 

cyanide 

Iso-nitrile 

C6H5— CN  +  2H2O        — »        C6H6— COOH 

Phenyl  cyanide  Benzoic  acid 

Acid  nitrile 

From  Diazo  Compounds. — The  diazo  compounds  may  also  be  used 
as  intermediate  products  to  obtain  the  acid  nitriles  and  thus  the  acids. 
The  reaction  already  discussed  under  diazo  compounds  (p.  599)  is  the 
Gattermann  reaction  with  cuprous  potassium  cyanide,  KCN.CuCN, 
by  which  the  diazo  group  is  replaced  by  the  cyanogen  group. 


C6H5i— N— (Cl  +  K)— CN.CuCN      >      C6H5— CN  +  N2 

1 1 1  Phenyl  cyanide 

Benzoic  nitrile 

IN 

Benzene 

diazonium 

chloride 

Ring  Carboxy  Acids  by  the  Grignard  Reaction. — Aromatic  acids 
with  carboxyl  in  the  ring  may  also  be  prepared  by  the  Grignard  reaction 


678  ORGANIC  CHEMISTRY 

by  the  direct  introduction  of  carbon  dioxide  into  an  aryl  magnesium 
halide,  Grignard  reagent. 

C6H5— I    +    Mg        >         C6H5— Mg— I  +  C02        > 

Phenyl  iodide  Magnesium 

phenyl  iodide 

(Grignard  reagent) 

C6H5— COO— Mgl  +  HO— H        — >     C6H5— COOH  +  HO— Mg— I 

Intermediate  Benzoic  acid 

product 

A  secondary  reaction  between  the  intermediate  product  and  the  Grig- 
nard reagent  causes  other  products,  alcohols  and  ketones,  to  be  formed 
at  the  same  time  especially  with  the  bromide  reagent. 

Synthesis  of  Side-chain  Carboxy  Acids. — The  side-chain  carboxy 
acids  being  really  aryl  substituted  aliphatic  acids  are  synthesized  by 
methods  characteristic  of  such  acids. 

From  Aryl  Halides. — The  most  important  method  has  already  been 
discussed,  viz.,  from  halogen  substituted  benzene  hydrocarbons  in 
which  the  halogen  is  in  the  side  chain.  This  side  chain  must  have  more 
than  one  carbon  group  otherwise  the  product  will  be  a  ring  carboxy  acid. 
The  halogen  compound  with  water  yields  the  hydroxyl  compound  or 
alcohol  and  if  the  halogen  and  therefore  the  hydroxyl  is  in  an  end  carbon 
group  the  resulting  alcohol  will  be  primary,  yielding  an  aldehyde  and 
then  acid  on  not  too  strong  oxidation.  If  the  oxidation  is  complete 
the  entire  chain  becomes  oxidized  to  carboxyl  and  a  ring  carboxy  acid 
results.  If  the  halogen  is  not  in  an  end  carbon  group  of  the  side  chain 
it  may  still  yield  an  acid,  not  by  conversion  into  the  alcohol,  aldehyde 
and  then  acid;  but  by  replacing  the  halogen  with  cyanogen  yielding 
an  acid  nitrile,  which  then,  on  hydrolysis,  gives  an  acid. 
In  this  case  the  carbon  groups  in  the  side  chain  become  increased  in 
number  by  one  so  that  this  method  may  be  used  in  case  the  side  chain 
has  only  one  carbon.  These  syntheses  may  be  illustrated  as  follows: 

C6H5— CH2— CH2(C1  +  H)— OH  > 

i-Chlor  2 -phenyl  ethane 

C6H5— CH2— CH2OH  C6H5— CH2— COOH 

2 -Phenyl  ethyl  alcohol  Phenylacetic  acid 

C6H5— CH2— CH(C12  +  2H)— OH        > 

i-Di-chlor  2 -phenyl 
ethane 

C6H5— CH2— CHO       jt_S        C6H5— CH2— COOH 

Phenyl  acet  Phenyl  acetic  acid 

aldehyde 


AROMATIC   ACIDS  679 

C6H5— CH2(C1  +  K)CN        > 

Benzyl  chloride 

C6H6— CH2— CN         +_f^2°         C6H5— CH2— COOH 

Benzyl  cyanide  Phenyl  acetic  acid 

(nitrile) 

C6H5— CH2(C1)— CH3+K)— CN > 

2 -Chlor  2-phenyl 
ethane 

C6H5— CH(CN)— CH3        +_£^°        C6H5— CH(COOH)— CH3 

2-Cyano  2-phenyl  2 -Phenyl  propionic 

ethane  acid 

C6H6— CH(C1)— COOH  +  K)— CN        > 

Phenyl  chlor  acetic  acid 

C6H5— CH(CN)— COOH        +J^°       C6H5— CH(COOH)— COOH 

Phenyl  malonic  Phenyl  ma  Ionic 

acid  nitrile  acid 

From  Aliphatic  Acids. — By  the  introduction  of  an  aryl  radical  into 
an  aliphatic  acid  we  may  obtain  side-chain  carboxy  acids  in  which 
the  side  chain  is  the  same  as  in  the  aliphatic  acid.  This  reaction  is 
effected  by  the  Friedel-Craft  reagent,  aluminium  chloride,  with  the 
aromatic  hydrocarbon  together  with  a  halogen  aliphatic  acid. 

C6H6— (H  +  HOOC— CH(C1)— CH2— COOH 

Benzene  Chlor  succinic  acid 

C6H6— CH— COOH 
CH2— COOH 

Phenyl  succinic  acid 

The  same  result  may  be  accomplished  by  using  an  aryl  halide  and 
copper  with  the  halogen  aliphatic  ester. 

C6H5— (Cl  +  Cu  +  Cl)— CH2— COOR        > 

Chlor  benzene  Chlor  acetic  acid 

(ester) 

C6H5— CH2— COOR        >        C6H5— CH2— COOH 

Phenyl  acetic  acid  Phenyl  acetic  acid 

(ester) 

With  Malonic  Ester. — The  malonic  ester  synthesis  (p.  274)  is  also 
applicable  in  this  case,  the  sodium  malonic  ester  reacting  with  aryl 
halides  just  as  it  does  with  alkyl  halides. 


68o 


ORGANIC  CHEMISTRY 


,COOC2H5 


C6H5—  CH2—  (Cl 

Benzyl  chloride 


Na)CH 


\:ooc2H5 

Sodium  di-ethyl 
malonate 


COOC2H5 
C6H5—  CH2—  CH<^ 

COOC2H5 

Phenyl  iso-succinic  acid 

(ethyl  ester) 

By  Grignard  Reaction.  —  Exactly  analogous  to  the  Grignard  synthe- 
sis of  ring  carboxy  acids  is  the  synthesis  of  side-chain  carboxy  acids 
by  the  introduction  of  carbon  dioxide  into  the  Grignard  reagent. 

Mg    -  >     C6H5—  CH2—  Mg—  Cl  +  CO2 


C6H5—  CH2—  Cl 

Benzyl  chloride 

C6H5—  CH2—  COO(Mg.Cl 

Intermediate  product 


C6H5—  CH2—  Mg—  Cl 

Magnesium  benzyl  chloride 

HO)—  H       -»     C6H5—  CH2—  COOH 

Phenyl  acetic  acid 


After  the  preceding  general  discussion  of  aromatic  acids  only  a  few 
of  the  many  that  are  known  need  to  be  discussed  in  detail  with  a 
consideration  of  their  derivatives.  Those  to  be  studied  are  : 

Ring  carboxy  acids 

Mono-basic,      Benzoic  acid,  C6H5  —  COOH 

COOH 
Di-basic,  Phthalic  acids,  C6H4<y 

XCOOH(o)(m)(p) 

Side-chain  carboxy  acids 
Saturated,        Phenyl  acetic  acid,  C6H5—  CH2—  COOH 

Hydro  cinnamic  acid,          C6H5—  CH2—  CH2—  COOH 
Unsaturated,    Cinnamic  acid  or  C6H5—  CH  =  CH—  COOH 

Phenyl  acrylic  acid 

Phenyl  propiolic  acid,          C6H5—  C  =  C—  COOH 
Phenyl  vinyl  acetic  acid,     C6H5—  CH  =  CH—  CH2— 

COOH 


Benzoic  Acid,  C3H5— COOH,  and  Derivatives 

Occurrence. — Benzoic  acid  is  a  naturally  occurring  substance  being 
found  both  free  and  as  esters  in  gum  benzoin,  Peru  and  Tolu  balsams, 
huckleberries,  the  flower,  dragon's  blood,  etc.  It  also  occurs  in  combina- 


BENZOIC   ACID    AND   DERIVATIVES  68 1 

tion  as  hippuric  acid  which  is  present  in  large  amounts  in  the  urine  of 
herbivorous  animals  and  in  very  small  amounts  in  human  urine. 
Benzoic  acid  is  of  especial  interest  historically  associated  with  benz- 
aldehyde  (p.  655)  because  of  Liebig  andWohler's  classic  investigation 
on  "The  Radical  of  Benzoic  Acid"  which  did  so  much  toward  estab- 
lishing the  theory  of  radicals  (p.  14).  It  is  a  solid,  crystalline  sub- 
stance forming  glistening  crystals,  m.p.  121°,  b.p.  249°.  It  sublimes 
below  its  melting  point  at  100°  and  is  also  volatile  with  steam,  the 
vapor  being  irritating.  It  is  soluble  in  375  parts  of  water  at  ordinary 
temperatures  and  in  45  parts  at  75°.  In  alcohol  and  ether  it  is  quite 
easily  soluble.  The  natural  sources  from  which  it  is  usually  obtained 
are  gum  benzoin  and  hippuric  acid.  From  the  former,  in  which  it  is 
present  in  the  free  condition,  it  is  obtained  by  heat,  the  acid  subliming; 
or  the  gum  is  heated  with  lime  in  which  case  the  acid  is  obtained  as  the 
calcium  salt  on  extraction  of  the  heated  mass.  To  get  the  acid  from 
hippuric  acid  the  latter,  which  is  an  acid  amide  derivative,  is  hydrolyzed 
with  dilute  acids,  the  benzoic  acid  being  thus  set  free. 

Syntheses. — The  important  synthetic  methods  for  its  preparation 
have  all  been  discussed  and  from  them  and  the  reactions  and  derivatives 
of  the  acid  its  constitution  has  been  fully  estalbished  as  mono-carboxy 
benzene. 

COOH 


C6H6— COOH         or 


Benzoic  acid 

The  syntheses  may  be  reviewed  by  simply  giving  the  reactions. 

+0 

From  Toluene,  CeHs— CH3  >  C6H5— COOH, 

Benzoic  acid 
+0 
From  Benzyl  alcohol,     C6H6— CH2OH  -- >  C6H6— COOH, 

Benzoic  acid 
.     +0 

From  Benzaldehyde,      C6H6— CHO  »  CeH5— COOH, 

Benzoic  acid 
+  H2O  +  O(HNO3) 

From  Benzyl  chloride,   C6H6— CH2C1  >  C6H6— COOH, 

Benzoic  acid 


682  ORGANIC  CHEMISTRY 

+  H20  +  O 
From  Benzal  chloride,    C6H5— CHC12  -- »•  C6H6— COOH, 

Benzole  acid 
+  2H20 
From  Benzo  trichloride,  C6H6— CC13  — >  C6HS— COOH, 

Benzole  acid 
+  2H20 

From  Phenyl  cyanide,   C6H5— CN  >  C6H5— COOH, 

Benzoic  nitrile,  Benzole  acid 

The  most  common,  synthesis  commercially  is  the  first  one  from  toluene 
either  by  direct  oxidation  or  through  one  of  the  intermediate  chlorides. 

In  its  chemical  properties  benzoic  acid  reacts  exactly  as  the  aliphatic 
mono-carboxy  acids  yielding  the  following  derivatives:  salts,  esters, 
acid  anhydride,  acid  chloride,  acid  amide,  acid  anilide,  benzoyl  deriva- 
tives, etc. 

Reduction. — On  reduction  with  sodium  the  acid  yields  the  corre- 
sponding alcohol,  benzyl  alcohol,  which  by  hydrogen  iodide  and  phos- 
phorus is  further  reduced  to  the  hydrocarbon  toluene.  This  last 
reducing  agent  also  reduces  the  acid  directly  to  the  hydrocarbon. 

C6H5— COOH  +  Na  +  H2O    >     C6H5— CH2OH 

Benzoic  acid  Benzyl  alcohol 

C6H5— COOH  +  HI  +  P         >     C6H5— CH3 

Benzoic  acid  Toluene 

Salts. — Most  of  the  salts  of  benzoic  acid  are  easily  soluble  com- 
pounds. Sodium  benzoate  is  used  as  a  preservative. 

Benzene  from  Benzoic  Acid. — Just  as  salts  of  acetic  acid  yield 
methane  by  the  loss  of  carbon  dioxide  when  heated  with  lime  so  benzoic 
acid  salts  yield  benzene. 

C6H5— COONa  +  Ca(OH)2    >    C6H6  +  CaCO3  +  NaOH 

Sodium  benzoate  Benzene 

Benzophenone  from  Benzoic  Acid. — Also  as  calcium  acetate  on 
heating  yields  acetone  so  calcium  benzoate  yields  diphenyl  ketone  or 
benzophenone. 

C6H5— (COO,  C6H5x 

>        )CO  +  CaC03 


C6H5— 

Calcium  benzoate  Benzophenone 

Esters. — The  esters  of  benzoic  acid  are  not  of  special  importance. 
The  methyl,  ethyl,  phenyl  and  benzyl  esters  are  found  in  certain  plants 


BENZOIC   ACID    AND    DERIVATIVES  683 

and  plant  resins.  They  all  have  pleasant  odors  and  are  formed  in 
making  qualitative  and  quantitative  determinations  of  the  acid. 

Benzoyl  Chloride. — The  acid  chloride  of  benzoic  acid,  benzoyl 
chloride,  CeH5 — CO — Cl,  is  readily  formed  by  the  action  of  phosphorus 
pentachloride  on  the  acid. 

C6H5— CO(OH  +  PC15    >     C6H5— CO— Cl  +  POC13  +  HC1 

Benzoic  acid  Benzoyl  chloride 

It  is  an  oily  liquid  with  a  strong  irritating  odor,  m.p.  — 1°,  b.p.  198°. 
With  alcoholic  hydroxyl  compounds  benzoyl  chloride  acts  exactly  as 
acetyl  chloride  does  and  the  benzoyl  group,  CeH5 — CO,  is  introduced 
in  place  of  the  hydroxyl  hydrogen  forming  esters. 

C6H5— CO(C1  +  H)O— C2H5    — *     C6H5— CO— OC2H5  +  H2O 

Benzoyl  chloride  Ethyl  alcohol  Ethyl  benzoate 

C6H5— CO— (Cl  +  H)O— CH2— C6H5 >  C6H5— CO— OCH2—  C6H5 

Benzoyl  chloride  Benzyl  alcohol  Benzyl  benzoate 

C6H5— CO— (Cl  +  H)O— C6H5    >    C6H5— CO— OC6H5 

Benzoyl  chloride  Phenol  Phenyl  benzoate 

Benzoylation. — The  introduction  of  the  benzoyl  radical  for  alcoholic 
hydrogen  is  termed  benzoylation  corresponding  to  acetylalion  or  th$ 
introduction  of  the  acetyl  radical  in  the  aliphatic  compounds.  The 
action  of  benzoyl  chloride  is  more  moderate  than  that  of  acetyl  chloride 
and  furthermore  the  products  are  often  crystalline  and,  therefore, 
readily  identified.  These  facts  often  make  it  more  desirable  to  ben- 
zoylate  an  hydroxyl  or  amino  compound  than  to  acetylate  it,  when  it  is 
necessary  to  know  whether  an  unknown  substance  is  an  alcoholic 
hydroxyl  compound  or  an  amino  compound,  and  how  many  of  such 
groups  are  present  (p.  318). 

Benzoic  Anhydride. — The  anhydride  of  benzoic  acid  is  exactly 
analogous  to  acetic  anhydride  and  is  formed  by  the  same  kind    of 
reaction. 
C6H5—  CO—  (Cl  +  Na)OOC— C6H5 >  C6H5— CO— O— OC— C6H5 

Benzoyl  chloride  Sodium  benzoate  Benzoic  anhydride 

In  the  aliphatic  series  acetylation  is  better  effected  by  means  of  acetic 
anhydride  than  of  acetyl  chloride.  With  the  benzene  compounds, 
however,  the  acid  chloride  is  better  than  the  anhydride. 

Benzoyl  Amino  Compounds. — Benzoyl  chloride  also  reacts  with 
ammonia,  aniline  and  amino  acids  yielding  acid  amide  compounds, 

C6H5—  CO—  (Cl  +  H)— NH2    — ->    C6H5— CO— NH2  +  HC1 

Benzoyl  chloride  Ammonia  Benzamide 


684  ORGANIC  CHEMISTRY 

C6H5—CO—  (Cl  +  H)NH—  C6H5    -  >     C6H5—  CO—  NH—  C6H5 

Benzoyl  chloride  Aniline  Benzanilide 

C6H5—  CO—  (Cl  +  H)—  NH—  CH2—  COOH  -  > 

Benzoyl  chloride  Amino  acetic  acid 

C6H5—  CO—  NH—  CH2—  COOH 

Benzoyl  amino  acetic  acid 
Hippuric  acid 

Schotten-Baumann  Reaction.  —  In  practice  these  reactions  take 
place  in  the  presence  of  sodium  hydroxide,  the  reaction  being  known  as 
the  Schotten-Baumann  reaction. 

Benzamide.  —  The  amide  of  benzoic  acid  is  formed  by  the  reaction 
given  above  and  also  by  the  action  of  chlor  formamide  on  benzene. 

C6H5—  (H  +  Cl)—  CO—  NH2    -  »    C6H5—  CO—  NH2 

Benzene  Chlor  formamide  Benzamide 

This,  it  will  be  recalled,  is  the  first  step  in  the  Gattermann  synthesis  of 
benzoic  acid  (p.  674).  Another  method  for  preparing  benzamide  is  by 
the  taking  up  of  water  by  benzoic  nitrile  which  is  in  agreement  with 
the  relation  of  these  compounds.  The  reaction  occurs  when  the  nitrile 
is  treated  with  an  alkaline  solution  of  hydrogen  peroxide. 


+  H2O    -  >     C6H5—  CO—  NH2 

Benzoic  nitrile  Benzamide 

Metal  Salts.  —  In  discussing  the  constitution  of  acet  amide  (p.  146) 
the  formation  of  metal  salts  raised  the  question  as  to  the  true  constitu- 
tion of  the  amide,  the  tautomeric  hydroxy  imide  formula  being  probable 
in  this  reaction. 


x 
.x  -  »     CH3 


Acet  amide  Sodium  acetamide 

(imide  form) 


Now  benzamide  forms  similar  metallic  salts  and  these  salts  when 
treated  with  alkyl  halides  yield  alkyl  amine  derivatives  of  benzoic  acid. 


v  v 

XNH2  XNH(Na  +  Cl)—  CH3 

Benzamide  Sodium  benzamide 


NH—  CH3 

Benzo  methyl  amide 


BENZOIC  ACID   AND   DERIVATIVES  685 

This  reaction  proves  that  in  the  sodium  benzamide  the  sodium  is 
linked  to  nitrogen  not  to  oxygen. 

Benzoyl  Phenyl  Urea.  —  When  this  sodium  salt  of  benzamide  is 
treated  with  iodine  two  sodium  atoms  are  lost  from  two  molecules,  a 
rearrangement  occurs  and  the  two  molecules  unite. 

/>  °\ 

CeHs  —  Cv        .  yC  —  CeHs     —  —  > 

XNH(Na  +  I2  +  Na)HNX 

Sodium  benzamide  -f  Iodine 

o         o 

C6H6—  C—  NH—  C—  HN  —  C6H6 

Benzoyl  phenyl  urea 

If  the  formula  is  written  differently  it  will  be  seen  better  as  a  urea 
derivative. 


—  C6H5  XNH—  C6H5  /NH2 

o=c  o=c(  P*CV 

XNH—  OC—  C6H5  XNH2  XNH2 

Benzoyl  phenyl  urea  Phenyl  urea  Urea 

Hofmann  Reaction.  —  The  metallic  salts  of  benzamide  are  also  in- 
volved in  the  Hofmann  reaction  (p.  148),  by  which  an  acid  amide  is 
converted  into  a  primary  amine. 

C6H5—  CO—  NH2  +  Br  +  KOH—  >C6H5—  CO—  NHBr  +  KOH  -  > 

Benzamide 

-KBr  and 
C6H5—  CO—  NKBr  —  >         C6H&—  N=C  =  O  +  H2O    -  > 


rearrangement       Phenyl  ^- 


C6H6—  NH2  +  CO2 

Phenyl  amine 
Aniline 


Benzanilide.  —  Analogous  to  benzamide  is  the  aniline  derivative  of 
benzoic  acid,  viz.,  benzanilide,  CeH6  —  CO  —  NH  —  CeHs,  which  is 
formed  by  the  reaction  previously  given  (p.  684)  from  benzoyl  chloride 
and  aniline. 

Beckmann  Rearrangement.  —  The  special  interest  in  connection 
with  this  compound  is  its  formation  from  benzophenone  oxime  by 
the  Beckmann  rearrangement  (p.  654). 


686  ORGANIC  CHEMISTRY 

CeHfi — C — CsHs  * 

II  + 

(O  H2)N— OH 

Benzophenone 

Beckmann  rearrangement 
C6H5— C— C6H5 >     C6H6— C— OH >     C6H6— C  =  O 

II  II  ! 

N— OH  N— C6H5  NH-C6H5 

Benzophenone  oxime  Benzanilide 

Hippuric  Acid. — When  the  benzoyl  group  is  introduced  into  an 
amino  acid  in  place  of  an  amino  hydrogen,  by  means  of  the  Schotten- 
Baumann  reaction,  a  benzoyl  amino  acid  is  obtained.  With  amino 
acetic  acid  or  glycine  (p.  388)  the  product  is  benzoyl  amino  acetic  acid 
or  benzoyl  glycine,  also  known  as  hippuric  acid. 

C6H5— CO— Cl  +  H)NH— CH2— COOH        > 

Benzoyl  chloride  Amino  acetic  acid 

Glycine 

C6H5— CO— NH— CH2— COOH 

Benzoyl  amino  acetic  acid 
Benzoyl  glycine 
Hippuric  acid 

When  hydrolyzed  with  dilute  potassium  hydroxide  the  products  are 
potassium   benzoate   and  glycine. 

—  CH2— COOH 

~ 

+  HO4-H 

Hippuric  acid 

C6H5— COOK  +  H2N— CH2— COOH 

Potassium  benzoate  Glycine 

Thus  both  by  its  synthesis  and  by  its  hydrolytic  products  hippuric  acid 
is  proven  to  be  benzoyl  glycine. 

As  early  as  1776  hippuric  acid  was  found  in  the  urine  of  cows,  and  in 
1829  Liebig  showed  that  it  was  a  benzoic  acid  derivative.  In  1846 
Dessaignes  established  its  constitution  as  benzoyl  glycine.  As  a 
natural  physiological  excretion  product  it  is  a  source  of  both  benzoic 
acid  and  of  glycine.  In  human  urine  it  is  present  to  the  amount  of 
about  0.7  gram  per  day,  i.e.,  about  0.05  to  0.07  per  cent.  The  amount 
excreted  per  day  may  be  noticeably  increased  by  eating  benzoic  acid 
or  other  compounds  which  can  yield  a  benzoyl  group,  e.g.,  cinnamic 
acid  or  toluene.  As  benzoic  acid  or  some  other  benzene  compound  is 
usually  present  in  plant  food  materials  and  as  glycine  is  a  product  of 


PHTHALIC   ACIDS   AND   DERIVATIVES  687 

protein  hydrolysis  the  hippuric  acid  in  the  animal  body  is  undoubtedly 
synthesized  from  these  two  sources  and  is,  therefore,  naturally  more 
abundant  in  the  urine  of  herbivorous  animals.  An  interesting  fact  in 
connection  with  the  physiological  synthesis  of  hippuric  acid  is  the  fact 
that  birds  which,  like  man,  normally  excrete  practically  no  hippuric 
acid,  when  fed  benzoic  acid  still  excrete  no  hippuric  acid.  Instead  a 
related  di-benzoyl  derivative  of  di-amino  valeric  acid  known  as 
ornithuric  acid  is  obtained.  From  this  it  would  appear  that  glycine  is 
not  a  protein  cleavage  product  in  birds  as  in  herbivorous  animals  and 
in  man. 

Toluic  Acids,  Xyloic  Acids,  Mesitylene  Carboxylic  Acid 

Mono-basic  ring  carboxy  acids  of  the  benzene  homologues  need 
only  to  be  mentioned. 


Toluene  yields  toluic  acids, 

XCOOH  (o)  (m)  (p) 

/CH3 
The  xylenes  yield  xyloic  acids,  C6H3^CH3 

XCOOH 

xCH3         (i) 

Mesitylene  yields  mesitylene  carboxylic  acid,     C6H2c; 

\      LH3          (5; 

XCOOH     (2) 

/COOH 
Phthalic  Acids,  C6H4v  ,  and  Derivatives 


The  only  other  ring  carboxy  acids  to  be  considered  in  detail  are  the 
three  phthalic  acids.  They  all  have  the  constitution  of  di-carboxy 
benzene,  CeH4  =  (COOH)2,  and  therefore  three  isomers  are  possible, 
ortho,  meta  and  para. 

Relation  to  Xylene. — Just  as  toluene,  mono-methyl  benzene,  on 
oxidation  of  the  methyl  group  to  carboxyl  yields  benzoic  acid,  mono- 
carboxy  benzone,  so  the  three  isomeric  xylenes,  di-methyl benzenes, 


688 


ORGANIC  CHEMISTRY 


yield  by  similar  oxidation  three  di-carboxy  benzenes,  with  the  three 
mono-carboxy,  or  toluic,  acids  as  intermediate  products. 


/ 


CH3 


C6H4v 

XCH- 

Xylenes 
o.-,  m.-,  p.- 


O 


+  0 


,COOH 


XCOOH 

Toluic  acids 
o.-,  m.-,  p.- 


C6H 


XCOOH 

Phthalic  acids 
o.-,  m.-,  p.- 


This  relation  of  the  three  phthalic  acids  to  the  three  xylenes  has  been 
fully  established  and  the  exact  constitution  of  each  set  of  isomers  is 
positively  proven.  This  has  been  dwelt  upon  in  our  general  discussion 
of  the  isomerism  of  di-substitution  products  of  benzene  and  of  the 
methods  of  orientation  by  which  the  position  of  the  substitution  groups 
is  determined  (p.  482).  The  full  constitution  and  names  of  the  three 
phthalic  acids  are : 

COOH  COOH  COOH 


COOH 


COOH 


o-Phthalic  acid 
Phthalic  acid 

m.p.  184 
(from  ortho-xylene) 


m-Phthalic  acid 
Iso-phthalic  acid 

m.p.  300 
(from  meta-xylene) 


COOH 

p-Phthalic  acid 
Terre -phthalic  acid 

m.p.  -(sublimes) 
(from  para-xylene) 


The  general  methods  for  synthesizing  ring  carboxy  acids  are  applicable 
to  the  phthalic  acids  if  we  start  with  the  corresponding  di-substituted 
benzenes  or  with  the  mono-substituted  benzoic  acids,  e.g., 

.COOH 


y(SO2OK- 

C6H/  +2K)CN 

X(SO2OK 

Benzene  di-sulphonic  acid 

(salt) 


C6H/      +4H20 

XCN 


Nitrile 


C6H 


COOH 


H20 


4\ 
X(Br 

Brom  benzoic  acid 


Na2  +  Cl)— COOC2H5 


C.H/ 

XCOOH 

Phthalic  acid 

.COOH 

"*   TJ  / 

^^4\ 

XCOOH 

Phthalic  acid 


Ethyl  chlor  formate 

Like  di-basic  acids  in  general  the  phthalic  acids  yield  both  mono-  and 
di-derivatives,  e.g.,  salts,  esters,  acid  chlorides,  acid  amides.  When 
heated  with  lime  the  acids  lose  two  molecules  of  carbon  dioxide  and 
yield  benzene  just  as  benzoic  acid  does  by  the  loss  of  one  molecule. 


PHTHALIC   ACIDS   AND   DERIVATIVES  689 

The  two  molecules  of  carbon  dioxide  may  be  lost  successively  and  ben- 
zoic  acid  will  be  obtained  as  an  intermediate  product. 

/(COO)H       -CO2  ,H  -C02  ,H 

CeH4v  CeH^v  CeH^ 

XCOOH  XCOOH  XH 

Phthalic  acids  Benzole  acid  Benzene 

(o)  (m)  (p) 

It  is  plain  that  the  three  isomeric  phthalic  acids  all  yield  the  same 
benzoic  acid,  there  being  only  one,  the  possibility  of  isomerism  dis- 
appearing as  soon  as  one  carboxyl  group  is  converted  into  hydrogen. 
If,  however,  the  phthalic  acids  are  reduced  and  the  carboxyl  groups 
converted  successively  or  together  into  aldehyde  or  primary  alcohol 
groups  and  finally  to  methyl  groups,  yielding  at  last  the  xylenes,  then 
isomerism  remains  throughout  the  series  of  products. 

ortho-Phthalic  Acid. — The  most  important  of  the  three  acids  is  the 
ortho -phthalic  acid  usually  termed  simply  phthalic  acid.  While  it 
may  be  prepared  by  the  general  methods  of  synthesis  the  most  impor- 
tant method  is  from  naphthalene.  This  method  is  important  both  com- 
mercially, as  in  the  synthesis  of  indigo  to  be  discussed  later  (p.  882), 
and  theoretically  in  connection  with  the  proof  for  the  constitution  of 
naphthalene.  The  reaction  can  not  be  written  or  explained  in  detail 
now,  but  will  be  studied  later  when  we  consider  naphthalene  itself 
(p.  766).  When  naphthalene,  which  is  a  hydrocarbon  of  a  series  re- 
lated to  benzene  and  which  has  the  composition  CioH8,  is  treated  with 
chlorine  an  addition  product  is  formed  and  then  oxidation  takes  place 
with  the  final  formation  of  ortho -phthalic  acid. 

+  O  ,COOH  (i) 

CioHg  +  Cl  CeH4K 

Naphthalene  XCOOH    (2) 

o-Phthalic  acid 

Phthalic  acid  is  a  crystalline  solid  which  melts  at  184°  with  the  loss 
of  water  and  the  formation  of  an  anhydride.  It  is  very  slightly  soluble 
in  cold  water,  but  quite  easily  soluble  in  hot  water  and  in  alcohol.  The 
loss  of  water  with  the  formation  of  an  anhydride  is  characteristic  of 
the  ortho -phthalic  acid  as  distinguished  from  the  meta-  and  para- 
phthalic  acids  which  do  not  yield  anhydrides. 

Phthalic  Anhydride. — In  speaking  of  the  formation  of  anhydrides 
from  the  di-basic  aliphatic  acids,  oxalic  acid,  malonic  acid,  succinic  acid , 

44 


6go 


ORGANIC  CHEMISTRY 


glutaric  acid  (pp.  281,  287),  we  found  that  anhydrides  are  formed  only 
in  the  case  of  those  acids  in  which  the  carboxyl  groups  are  in  close 
proximity  to  each  other  in  space,  as  explained  by  the  tetrahedral  car- 
bon atom.  Such  a  condition  exists  in  the  cases  of  succinic  acid  and 
glutaric  acid,  both  of  which  readily  form  anhydrides,  but  not  in  the 
cases  of  oxalic  and  malonic  acids,  neither  of  which  yield  anhydrides. 
Now  if  we  examine  the  formula  of  ortho-phthalic  acid  we  shall  find  that 
exactly  the  same  space  relationship  of  the  two  carboxyl  groups  exists 
in  it  as  in  succinic  acid,  and  in  fact  both  yield  anhydrides  as  follows: 

H2C— CO(OH)      -H20     H2C— COX 

I  > 

H2C— COO(H)  H2C— COT 


Succinic  acid 


Succinic  anhydride 


C— CO(OH)      -H20 
C— COO(H) 


C 
H 

Phthalic  anhydride 

In  each  case  the  two  carboxyl  groups  form  the  ends  of  a  four  carbon 
chain  and  from  the  tetrahedral  models  of  carbon  atoms  it  will  be  seen 
that  hydroxyl  groups  linked  to  the  end  carbons  of  a.  four  or  jive  carbon 
chain  are  in  very  close  proximity.  In  such  cases  loss  of  water  takes 
place  easily  and  an  anhydride  results.  The  additional  fact  that 
neither  meta-phthalic  acid  nor  para-phthalic  acid  do  form  anhydrides 
strengthens  the  correctness  of  the  explanation  and  the  truth  of  the 
tetrahedral  theory.  In  both  of  these  acids  the  carboxyl  groups  are 
not  thus  situated  in  relation  to  each  other,  being  much  further  apart, 
even  in  the  meta  compound,  and  they  do  not  lose  water.  Phthalic 
anhydride  is  a  beautiful  crystalline  compound  forming  long  white 
needles,  m.p.  128°.  When  treated  with  water  alone  the  anhydride  is 
only  slightly  reconverted  into  the  acid,  but  when  treated  with  alkalies 
it  readily  forms  salts  of  the  acid.  Phthalic  anhydride  is  the  most  im- 
portant derivative  of  the  phthalic  acids,  being  of  especial  importance 


PHTHALIC   ACIDS    AND    DERIVATIVES  691 

in  the  synthesis  of  some  valuable  dyes  known  as  phthaleins.  When 
phthalic  anhydride  is  heated  with  phenol  the  common  indicator  phenol 
phthalein  is  obtained  which  is  one  of  the  phthalein  dyes.  This  and 
related  compounds  will  be  considered  later  (p.  750). 

Phthalimide. — Phthalic  anhydride  also  yields  other  derivatives, 
viz.,  phthalimide  and  phthalyl  chloride.  When  phthalic  anhydride 
is  treated  with  ammonia  a  compound  is  formed  by  replacement  of  the 
anhydride  oxygen  with  the  imide  group,  (  =  NH), 

/C0\  /CO\ 

C6H4<        >(0  +  H2)NH  ->         C6H4<         >NH 

XXX  \C(X 

Phthalic  anhydride  Phthalimide 

This  is  analogous  to  the  formation  of  succinimide  from  succinic  anhy- 
dride (p.  284). 

CH2— COX  CH2— CO 


CH2— CO  CH2— CC 

Succinic  anhydride  Succinimide 

Phthalimide  is  a  crystalline  compound  which  may  be  sublimed,  m.p. 
233-5°-  With  ammonia  it  yields  the  di-amide  of  phthalic  acid, 
phthalamide. 

+NH3  CO(NH2) 

C6H/ 

XCONH(H) 

Phthalimide  Phthalamide 

This  shows  that  phthalimide  is  a  compound  of  an  anhydride  type 
formed  by  loss  of  ammonia  from  phthalamide  just  as  phthalic  anhy- 
dride is  formed  from  phthalic  acid  by  the  loss  of  water.  Like  other 
acid  amides  and  imides  phthalimide  forms  salts  by  replacement  of  the 


imide  hydrogen  by  metals,  e.g.,  potassium  phthalimide,  C6H4\          yNK. 
With  alkyl  halides  these  salts  yield  alkyl  phthalimides. 


C6H4<  N(K  +  I)—  C2H5         -  >        C6H4<  N—  C2H5 

XCO/  \CO/ 

Potassium  phthalimide  Ethyl  iodide  Ethyl  phthalimide 


692  ORGANIC  CHEMISIRY 

With  ethylene  bromide,  i-2-di-brom  ethane,  two  molecules  of  the 
phthalimide  become  linked  by  the  ethylene  group. 

/co\  x°c\ 

C6H4<        >N(K  +  Br)—  CH2—  CH2—  (Br  +  K)N<        >C6H4  --  > 
\CO/  \OC/ 


Phthalimide  Ethylene  bromide  Phthalimide 

(Salt)  (salt) 


/\ 

N—  CH2—  CH2—  N<         > 
XXX 


N—  CH2—  CH2—  N<         >C6H 

Ethylene  phthalimide 


On  hydrolysis  these  compounds  split  so  that  the  nitrogen  remains  linked 
to  the  aliphatic  chain  as  an  aliphatic  amine  and  phthalic  acid  is  re- 
formed, with  phthalic  anhydride,  probably,  as  an  intermediate  step. 

/COk  Xco\ 

C6H4<       :>N—  C2H5     -  >     C2H5—  NH2  +  C6H4<        >O  +  H2O 

\COr     -U  Ethyl  amine  \CO/ 

Phthalic  anhydride 

.Oi  =  H2 

Ethyl  phthalimide 


OOH 

Phthalic  acid 


N—  CH2—  CH 

XX 

Ethylene  phthalimide 


/°C\ 

N<        >C6H4 


/COOH 
2C6H4<  +  H2N—  CH2—  CH2—  NH2 

^COOH  i-2-Di-amino  ethane 

Phthalic  acid 

Phthalyl  Chloride.  —  When  phthalic  anhydride  is  treated  with 
phosphorus  pentachloride,  in  the  proportion  of  one  molecule  of  each, 
two  chlorine  atoms  replace  one  oxygen  atom  and  a  compound  is  formed 
known  as  phthalyl  chloride,  an  oily  liquid,  m.p.  o°,  b.p.  275°.  Two 
structures  are  possible  for  this  chloride. 

/COC1  /CC1 

4<  or  C6H4< 

\COC1  \CO 

Phthalic  anhydride  (Sym.)  Phthalyl  chloride         (Unsym.) 

-f  POC13 


/  /2\ 

+  PC15    -  >     C6H4<  or  C6H4<  >0 

\  \        / 


PHTHALIC   ACIDS    AND    DERIVATIVES  693 

It  will  be  recalled  that  in  the  case  of  succinyl  chloride  both  of  these 
forms  are  obtained,  but  mostly  the  symmetrical  (p.  282).  Now  from 
phthalic  anhydride  only  one  phthalyl  chloride  is  obtained.  This  chlo- 
ride acts  like  the  unsymmetrical  succinyl  chloride,  not  like  the  symmet- 
rical. The  positive  proof,  however,  that  phthalyl  chloride  is  the  un- 
symmetrical compound  is  the  following:  Sodium  amalgam  reduces 
phthalyl  chloride  by  replacement  of  the  chlorine  with  hydrogen.  The 
compound  formed  is  known  as  phthalide.  This  phthalide  takes  up 
water  as  anhydrides  do  and  the  product  is  hydroxy-methyl  benzole 
acid. 


CC12  +  H  /CH2\         +H20  XCH2OH 

C«H/          V)          ~*      C6H/         \)          —      C6H/ 

NCO/  XCCT  XCOOH 

Phthalyl  chloride  Phthalide  Hydroxy-methyl 

benzoic  acid 

From  these  relationships  it  is  seen  that  phthalyl  chloride  must  have 
the  unsymmetrical  formula. 

meta-  and  para-Phthalic  Acids.  —  Little  need  be  said  in  regard  to 
the  other  two  phthalic  acids.  The  meta  compound,  known  more  com- 
monly as  iso-phthalic  acid,  is  a  solid  which  crystallizes  in  needles, 
m.p.  300°.  It  sublimes  without  losing  water  not  yielding  an  anhydride. 
It  is  prepared  from  meta-xylene  or  from  meta-toluic  acid.  The  para 
acid,  better  known  as  terre  -phthalic  acid,  is  a  crystalline  compound 
which  sublimes  without  melting  and  without  yielding  an  anhydride. 
It  is  prepared  from  para-xylene,  para-toluic  acid  or  cymene,  para- 
methyl  iso-propyl  benzene,  also  from  turpentine  which  is  related  to 
cymene  (p.  817). 

Hydro  Phthalic  Acids.  —  An  important  set  of  derivatives  of  the 
phthalic  acids  may  be  mentioned  here  although  they  really  belong  to 
another  series  of  compounds.  These  are  the  hydro  phthalic  acids 
which  are  hydrogen  addition  products  .  It  will  be  recalled  that  benzene 
takes  up  by  addition  either  two,  four  or  six  hydrogen  (or  bromine)  atoms 
forming  di-hydro  benzene,  tetra-hydro  benzene  or  hexa-hydrc  ben- 
zene, the  last  being  cyclo-hexane  or  hexa-methylene  (p.  468).  For  each 
addition  of  two  hydrogens  one  of  the  double  bonds  of  the  benzene  ring 
is  changed  to  a  single  bond.  Now  the  phthalic  acids  yield  an  analogous 
series  of  hydrogen  addition  products. 


694 


HC 


ORGANIC  CHEMISTRY 

COOH 
CH 


COOH 

Terre-phthalic  acid 


CH 

I 
COOH 

Di-hydro  terre-phthalic  acid 


COOH 

Tetra-hydro'terre 
phthalic  acid 


COOH 

Hexa-hydro  terre- 
phthalic  acid 


The  hexa-hydro  product  is  plainly  a  di-carboxyl  derivative  of  hexa- 
methylene  and  thus  belongs  really  to  the  poly-methylene  series  of  com- 
pounds and  strictly  speaking  should  not  be  included  here  as  we  have 
said.  It  will  be  seen  that  in  the  cases  of  the  di-hydro  and  tetra-hydro 
products  structural  isomerism  will  occur  depending  upon  the  positions, 
relative  to  the  carboxyl  group,  which  the  added  hydrogens  take,  or  in 
other  words,  the  position  which  the  remaining  double  bonds  occupy. 
This  isomerism  will  be  referred  to  in  other  connections.  In  the  case 
of  the  hexa-hydro  product  all  the  positions  are  occupied  by  an  added 
hydrogen,  no  double  bond  remains  and,  therefore,  no  structural  iso- 
merism is  possible.  The  hexa-hydro  terre-phthalic  acid,  however, 
exhibits  a  case  of  stereo-isomerism  of  the  geometric  type  as  shown  in 
the  following  formulas: 


PHTHALIC   ACIDS   AND   DERIVATIVES 

H— C— COOH          H— C— COOH 


695 


H-cn 

H2C^J 


CH2 


H— C— COOH       HOOC— C— H 

(cis  form)  (trans  form) 

Hexa -hydro  terre-phthalic  acid 

These  geometric  stereo-isomers  are  analogous  to  the  similar  forms  in 
the  case  of  maleic  acid,  (cis),  and  fumaric  acid,  (trans),  and  take  the 
same  distinguishing  names. 

Uvitic  Acid,  Tri-mesitic  Acid,  Mellitic  Acid 

A  few  other  poly-basic  ring  carboxy  acids  may  be  mentioned  by  name 
and  formula  only.  Mesitylene,  i-3-5-tri-methyl  benzene,  yields  a 
di-carboxy  and  tri-carboxy  acid  together  with  a  mono-carboxy  acid 
already  referred  to. 


CH3 


COOH 


H3Cl  JCH3 

Mesitylene 


Mesitylenic  acid 


COOH 


COOH 


H3CL  JCOOH  HOOCL  JCOOH 

Uvitic  acid  Trimesitic  acid 

A   hexa-carboxy   acid   is   also   known,   viz.,  mellitic   acid   or  hexa- 
carboxy  benzene. 

COOH 


HOOcl     JcOOH 


COOH 

Mellitic  acid 


696 


ORGANIC  CHEMISTRY 


It  is  found  in  nature  as  a  mineral,  in  the  form  of  an  aluminium  salt 
known  as  honey  stone  or  mellite.  It  is  formed  when  graphite  is 
oxidized  with  nitric  acid  and  it  may  be  synthesized  by  oxidizing  hexa- 
methyl  benzene. 

Phenyl  Acetic  Acid,  C6H5—  CH2—  COOH,  Carboxy-methyl  Benzene 

This  acid  is  the  simplest  aromatic  acid  with  the  carboxyl  in  the  side 
chain.  Its  name,  phenyl  acetic  acid,  indicates  the  relation  to  the 
aliphatic  acids  as  a  phenyl  derivative.  The  commonly  used  names  for 
the  side-chain  carboxy  acids  are  derived  similarly,  e.g.,  phenyl  propiolic 
acid.  It  will  be  seen  at  once  that  phenyl  acetic  acid  and  the  toluic  acids 
are  isomeric,  the  first  being  the  result  of  the  partial  oxidation  of  ethyl 
benzene,  the  latter  the  result  of  the  partial  oxidation  of  the  di-methyl 
benzenes  or  xylenes  which  are  isomeric  with  ethyl  benzene.  In  both 
cases  the  relationship  to  the  hydrocarbon  is  that  only  one  carbon  group 
of  the  side  chain  is  oxidized  to  carboxyl. 


CH3      +O 


CeH^x 

XCH3 

Xylenes 

C6H5—  CH2—  CH3 

Ethyl  benzene 


CH3          +0 
-  > 
COOH 

Toluic  acids 


C6H5—  CH2—  CH2OH 

Phenyl  ethyl  alcohol 

C6H5—  CH2—  COOH 

Phenyl  acetic  acid 


4v 
N 


COOH 


COOH 

Phthalic  acids 


+0 


+0 


C6H5—  COOH 

Benzole  acid 


On  further  oxidation  to  the  final  product  all  the  carbon  groups  of  the 
side  chain  are  completely  oxidized  and  the  products  are  as  above, 
the  dimethyl  benzenes  and  toluic  acids  yielding  di-carboxyl  ring  acids 
while  ethyl  benzene  and  phenyl  acetic  acid  yield  the  mono-carboxyl 
ring  acid.  This  realtionship  shows  clearly  the  difference  in  character 
between  a  ring  carboxyl  acid  and  an  isomeric  side-chain  carboxyl  acid. 
Because  of  its  isomerism  with  toluic  acid  phenyl  acetic  acid  is  also  known 
as  alpha-toluic  acid,  a  name  that  does  not  seem  advisable.  While 
phenyl  acetic  acid  is  not  of  especial  importance,  the  other  side-chain 
carboxyl  acids  which  we  shall  mention  are  of  considerable  importance. 


CINNAMIC   ACIDS  697 

Hydrocinnamic  Acid  and  Cinnamic  Acid 


The  next  higher  homologous  side-chain  carboxyl  acid  is  the  one  in 
which  the  side  chain  has  three  carbon  groups,  CeH5 — CH2 — CH2 — 
COOH.  It  is,  therefore,  beta-phenyl  propionic  acid  or  i-carboxy 
2-phenyl  ethane.  It  is  commonly  known  as  hydrocinnamic  acid 
because  of  its  relation  to  cinnamic  acid  as  the  hydrogenated  or  reduction 
product.  In  the  aliphatic  series  we  have  two  acids,  one,  propanoic 
acid  or  propionic  acid,  the  other  propenoic  acid  or  acrylic  acid.  They 
are  related  to  each  other  as  corresponding  saturated  and  unsaturated 
compounds  (p.  172).  The  latter,  acrylic  acid,  yields  propionic  acid  on 
reduction  by  the  addition  of  two  hydrogen  atoms  and  the  conversion  of 
the  unsaturated  chain  into  a  saturated  one. 

-2H 
CH3— CH2— COOH    ^ZH    CH2  =  CH— COOH 

Propionic  acid  i      TT  Acrylic  acid 

Now  hydrocinnamic  acid  bears  exactly  the  same  relationship  to  cin- 
namic acid,  the  former  being  phenyl  propionic  acid,  the  latter  phenyl 
acrylic  acid. 

-2H 
C6H5— CH2— CH2— COOH    ZZ±    C6H5— CH  =  CH— COOH 

Hydrocinnamic  acid  I      TT  Cinnamic  acid 

beta-Phenyl  propionic  acid  beta-Phenyl  acrylic  acid 

It  may  be  well  to  mention  here  another  acid  already  discussed,  the  name 
of  which  indicates  a  similar  and  yet  distinctly  different  relationship 
from  that  indicated  by  the  name  hydrocinnamic  acid.  This  acid  is 
hydracrylic  acid  (p.  245).  It  is  related  to  acrylic  acid  as  follows: 

-H20 
CH2OH— CH2— COOH      ZZZ!       CH2  =  CH— COOH 

Hydracrylic  acid  4- H  O  Acrylic  acid 

Here  the  relationship  is  that  of  loss  or  addition  of  water,  the  name 
hydr-acrylic  meaning  hydrated  acrylic,  whereas  the  relationship  between 
cinnamic  acid  and  hydrocinnamic  is  loss  or  addition  of  hydrogen,  the 
name  hydro-cinnamic  meaning  hydrogenated  cinnamic.  The  same 
relationship  is  expressed  in  the  case  of  propionic  acid  if  we  name  it 
hydro -acrylic  acid. 

Malonic  Ester  Synthesis  of  Hydrocinnamic  Acid . — While  hydro- 
cinnamic acid  is  usually  prepared  by  the  reduction  of  cinnamic  acid  it 


698  ORGANIC  CHEMISTRY 

may  also  be  prepared  by  the  malonic  ester  synthesis  (p.  274)  from 
benzyl  chloride. 

COOC2H5 
C  6H5—  CH2—  (Cl  +  Na)  H(\  -» 

Benzyl  chloride  XCOOC2H5 

Sodium  di-ethyl 
malonate 


C6H6—  CH2—  CH  +    2H20 

XCOOC2H5 

Intermediate  ester 

(COO)H      (-C02at  1  80°) 
C6H6—  CH2—  CH<^ 

XCOOH 

beta-Phenyl  methyl  malonic  acid 


g—  CH2—  CH2—  COOH 

Hydrocinnamic  acid 

Cinnamic  Acid  by  Perkin's  Reaction.  —  Cinnamic  acid  has  the  con- 
stitution assigned  to  it  above  as  is  proven  by  the  following  synthesis 
from  benzaldehyde  by  condensation  with  sodium  acetate  in  the  pres- 
ence of  acetic  anhydride. 

C6H5—  CH  =  (O  +  H2)  =  CH—  COONa        -  > 

Benzaldehyde  Sodium  acetate 

C6H5—  CH  =  CH—  COONa  +  H2O 

Cinnamic  acid  (salt) 

The  reaction  is  known  as  Perkin's  reaction  and  is  applicable  to  the 
preparation  of  any  unsaturated  acid,  and  is  especially  used  in  the  ben- 
zene series.  By  using  salts  of  different  aliphatic  acids  in  place  of  acetic 
acid  any  desired  product  may  be  obtained.  The  aldehyde  may  also  be 
varied,  but  the  aldehyde  group  must  be  linked  to  the  ring.  Also  in  case 
of  aliphatic  acids  containing  several  carbon  groups  the  condensation 
-  of  the  aldehyde  always  takes  place  with  the  carbon  group,  (CH2), 
which  is  linked  to  the  carboxyl.  The  reaction  probably  takes  place 
like  the  aldol  condensation  (p.  116),  yielding  a  hydroxy  acid  as  an 
intermediate  product,  which  then  loses  water,  yielding  the  unsaturated 
acid. 

Isomerism.  —  Cinnamic  acid  occurs  as  geometric  stereo-isomers,  i.e., 
as  cis  and  trans  forms  like  maleic  and  fumaric  acids  (p.  291)  and 
crotonic  and  iso-crotonic  acids  (p.  177).  This  is  apparent  as  it  is 


CINNAMIC  ACIDS  699 

the  phenyl  analogue  of  crotonic  acid,  cinnamic  acid  being  beta-phenyl 
acrylic  acid  and  crotonic  acid  beta-methyl  acrylic  acid.  The  two  forms 
are  as  follows: 

C6H6—  C— H  C6H5— C— H 

II  II 

HOOC— C— H  H— C— COOH 

(cis  form)  (irons  form) 

Cinnamic  and  Allo -cinnamic  acids 

Which  of  the  two  is  the  cis  form  and  which  the  trans  form  has  not  been 
determined.  A  third  cinnamic  acid,  viz.,  iso-cinnamic  acid,  is  also 
known,  but  the  constitution  of  it  has  not  been  established.  Cinnamic 
acid  is  found  in  nature  in  the  resin  storax  both  as  the  free  acid  and  as 
the  cinnamic  alcohol  ester,  styrin.  It  is  also  found  in  Peru  and  Tolu 
balsams  as  the  free  acid  and  as  the  benzyl  alcohol  ester,  the  benzoic 
acid  ester  of  benzyl  alcohol  being  present  also.  Thus  benzyl  alcohol, 
benzoic  acid,  cinnamic  alcohol  and  cinnamic  acid  are  all  constituents  of 
esters  present  in  these  plant  resins.  Allo -cinnamic  acid,  the  geometric 
isomer,  is  obtained  from  coca  leaves  from  which  the  alkaloid  cocaine  is 
also  obtained  (p.  896).  When  cinnamic  acid  is  heated  with  lime  it 
loses  carbon  dioxide  and  yields  the  unsaturated  side-chain  hydrocarbon 
styrene,  or  phenyl  ethylene,  CeHs — CH  =  CH2.  On  reduction  it  yields 
first  cinnamic  aldehyde,  found  in  oil  of  cinnamon  (p.  842)  and  then 
cinnamic  alcohol.  Both  cinnamic  acid  and  allo-cinnamic  acid  yield 
anhydrides. 

Atropic  Acid. — A  structural  isomer  of  cinnamic  acid  is  an  acid  ob- 
tained by  loss  of  water  from  tropic  acid  and,  therefore,  known  as  atropic 
acid.  It  has  been  shown  to  be  the  alpha  isomer  of  cinnamic  acid,  i.e., 
alpha-phenyl  acrylic  acid,  C6H5 — C  =  CH2.  Tropic  acid  is  a 

COOH 

constituent  of  the  alkaloid  atropine  which  is  related  to  cocaine,  the 
alkaloid  of  coca  leaves,  which  also  yields  allo-cinnamic  acid.  Such 
facts  in  regard  to  the  natural  occurrence  of  related  compounds  are  of 
great  interest  and  undoubtedly  of  special  biological  significance  of  which 
only  little  is  yet  known.  The  alkaloids  referred  to  will  be  studied 
later  (p.  886). 


700  ORGANIC  CHEMISTRY 

Other  Unsaturated  Side-chain  Carboxy  Acids 

Phenyl  Crotonic  Acid.  Phenyl  Vinyl  Acetic  Acid. — A  phenyl  de- 
rivative of  cro tonic  acid  is  known,  C6H5—  CH2— CH  =  CH— COOH, 
beta-benzyl  acrylic  acid.  Also  the  structural  isomer  of  crotonic  acid, 
viz.,  vinyl  acetic  acid,  CH2  =  CH — CH2 — COOH,  yields  a  phenyl  deriva- 
tive, CeHs— CH  =  CH— CH2— COOH,  phenyl  vinyl  acetic  acid  or 
i -phenyl  Ai-butenoic-4  acid,  which  is  important  in  connection  with  the 
constitution  of  naphthalene  (p.  768). 

Phenyl  Propiolic  Acid. — The  acetylene  unsaturated  side  chain 
hydrocarbon  phenyl  propine,  C6H6 — C  =  C — CH3,  yields  an  acid  known 
as  phenyl  propiolic  acid,  C6H5 — C  =  C — COOH,  which  by  loss  of  car- 
bon dioxide  yields  phenyl  acetylene,  C6H6 — C  =  CH.  The  acid  is  im- 
portant in  connection  with  the  synthesis  of  indigo  (p.  879). 


X.  SUBSTITUTED  AROMATIC  ACIDS 

The  different  kinds  of  substitution  products  of  the  aromatic  acids 
which  it  is  possible  to  obtain  are  very  numerous.  Without  reference 
to  the  particular  element  or  group  which  is  substituted  we  may  have  the 
following  types. 

Ring  carboxy  acids: 

,COOH 

Substitution  in  the  ring,  e.g.,  C6H4^  lodo  benzole  acid 

XI 

,COOH      Hydroxy-methyl 

Substitution  in  the  side  chain,  e.g.,  CftH4^  benzole  acid 

XCH2OH 

Side-chain  carboxy  acids: 

=  CH—  COOH      Nitro 


, 

Substitution  in  the  ring,  e.g.,  C6H4  cinnamic  acid 


Substitution  in  the  side  chain,  e.g.,  C6H5—  CH2—  CH(NH2)—  COOH 

Phenyl  alanine 

2—  CH(NH2)—  COOH 


, 

Substitution  in  the  ring  and  side  C6H4^  Tyrosine 

chain,  e.g.,  OH 

Mixed  ring-carboxy  and  side-chain  carboxy  acids: 

,COOH          Phenyl  glycine 
C6H4/  o-carboxylic  acid 

XNH—  CH2—  COOH 

The  general  methods  of  synthesis  of  all  these  types  are  two:  (i)  From 
the  acid  itself  by  direct  substitution  of  the  desired  element  or  group  into 
ring  or  side  chain.  This  method  will  vary  according  to  whether  the 
substitution  is  in  the  ring  or  side  chain,  and  whether  the  side  chain  is 
saturated  or  unsaturated.  (2)  From  a  substituted  hydrocarbon,  nitrite, 
amine,  etc.,  and  the  conversion  of  this  into  the  acid  by  one  of  the 
methods  already  discussed  under  the  synthesis  of  acids. 

701 


702  ORGANIC  CHEMISTRY 

While  the  known  compounds  representing  the  various  types  are 
many  only  a  relatively  few  will  be  considered  individually.  These 
will  include  those  which  are  important  in  themselves  or  that  are  related 
to  other  important  compounds  which  have  already  been  studied  or  that 
will  be  studied  later.  Some  members  of  the  class  not  mentioned  now 
may  be  referred  to  later,  in  their  proper  connection  in  relation  to  some 
important  product.  At  the  outset  in  considering  a  large  class  such  as 
the  one  which  we  are  discussing  it  is  well  to  make  a  survey  of  the  theo- 
retical possibilities  for  they  are  not  simply  theoretical  possibilities 
but  have  become  actual  facts  established  by  the  study  of  definite 
compounds. 

RING  SUBSTITUTED  RING  CARBOXY  ACIDS 

Let  us  now  examine  the  conditions  to  be  met  in  applying  either 
of  the  two  general  methods  just  given  to  the  formation  of  a  substi- 
tuted ring-carboxy  acid  in  which  the  substitution  also  is  to  be  in 
the  ring. 

Influence  of  Carboxyl. — The  first  condition  is  that  the  presence  of 
a  carboxyl  group  in  the  ring  has  a.  decided  influence  on  the  further  ring- 
substitution  of  the  compound.  We  have  stated  before  that  in  general 
the  presence  of  an  element  or  group  in  the  benzene  ring  makes  the 
introduction  of  a  second  one  much  more  easy.  Benzoic  acid,  therefore, 
just  like  toluene,  is  more  easily  nitrated  or  sulphonated,  for  example, 
than  is  benzene.  The  presence  of  the  carboxyl  group  also  determines 
the  position  which  a  second  substituting  group  usually  enters.  We 
have  given  the  following  as  the  general  rule  (p.  506).  When  a  benzene 
ring  has  already  substituted  in  it  a  halogen  element,  (CL,  Br),  an 
amino,  ( — NH2) ,  hydroxyl,  (OH),  or  methyl,  (CH3),  group  then  a  second 
element  or  group  substituted  by  direct  action  usually  enters  both  the 
para  and  ortho  positions,  the  former  usually  in  larger  amount,  but  not 
the  meta.  On  the  other  hand,  when  the  original  substituted  group 
is  an  aldehyde,  ( — CHO),  carboxyl,  ( — COOH),  cyanogen,  ( — CN),  nitro, 
( — NO2),  or  sulphonic  acid,  ( — SO2OH),  group  then  a  second  element  or 
group  substituted  by  direct  action  usually  enters  the  meta  position. 
Therefore  when  a  substituted  acid  is  made  by  direct  substitution  of  a 
ring-carboxy  acid  itself  we  usually  obtain  the  meta  compound.  In  order 
to  prepare  the  ortho  and  para  compounds  we  must  use  the  second 
general  method  of  indirect  substitution,  viz.,  starting  with  a  hydrocar- 


SUBSTITUTED    AROMATIC   ACIDS  703 

bon,  phenol  or  amine,  we  introduce  the  desired  group  and  then  con- 
vert the  substituted  compounds,  which  will  be  the  ortho  and  para,  into 
the  acid  by  appropriate  reactions.  This  may  be  illustrated  as  follows: 

.COOH  COOH  (i) 

C6R/  +HO)— SO2OH  — >        C6H4<^ 

(H  XS02OH(3) 

Benzoic  acid  m-Sulpho  benzoic  acid 

sCH*  CH3      (i) 

X(H  +  HO)— SO2OH  \O2OH(2),  (4) 

Toluene  o-,  p-Toluene  sulphonic 

acid 

COOH  (i) 
S02OH  (2)  (4) 

o-,  p-Sulpho 
/  benzoic  acid 

As  both  nitration  and  sulphonation  take  place  with  comparative  ease, 
with  either  hydrocarbons  or  acids,  and  as  the  nitro  compounds  yield 
amino  compounds  and  these  yield  diazo  compounds,  with  their  numer- 
ous reactions,  in  particular  the  Sandmeyer  reaction  for  obtaining 
nitriles;  and  as  sulphonic  acids  are  easily  converted  into  phenols  or 
nitriles;  it  will  be  seen  that  by  a  combination  of  these  synthetic  reac- 
tions practically  any  desired  ring-substituted  mono-basic  or  poly- 
basic  ring-carboxy  acid  may  be  obtained. 

Classified  according  to  the  character  of  the  substituting  element  or 
group  the  substituted  aromatic  acids  may  be  put  in  the  following 
classes,  embracing  all  of  the  types  previously  given  with  one  exception. 
Taking  for  illustration  the  ring-substituted  ring-carboxy  acids  and 
using  benzoic  acid  as  our  example  we  have : 

COOH 

Halogen  acids,  e.g.,     CeH4\' 

XCl(Br.I) 
COOH 
Nitro  acids,  e.g.,     CeH4<f 

XNO2 

COOH 
Amino  acids,  e.g.,     CeH4<T 

XNH2 


704  ORGANIC  CHEMISTRY 

COOH 

Sulpho  acids,  (mixed    e.g.,     CeH4<f 
sulphonic  acids  and  SO2OH 

carboxy  acids) 

COOH 
Hydroxy  acids,  e.g.,     CeH4<^ 

XOH 

The  last  three  are  by  far  the  most  important. 

HALOGEN  AROMATIC  ACIDS 

The  halogen  ring-substituted  acids  are  prepared  by  some  one  of  the 
general  methods  of  synthesis,  depending  on  whether  the  desired  product 
is  the  ortho,  meta  or  para  compound.  The  meta  acids  are  made  by 
direct  action  of  a  halogen  on  the  aromatic  acid. 

COOH  XCOOH  (i) 

C6H/  +  Br)—  Br  -»         C6H4< 

i  \K  Br 

Benzoic  acid  m-Brom  benzoic  acid 

The  para  acids  are  usually  made  by  halogenating  a  hydrocarbon  and 
then  oxidizing  the  side  chain  to  carboxyl. 


7  CH3  COOH  (i) 

c6H4<(     +  ci)—  ci     ->   c6H4<(        _:;   c6H/ 

(H  XC1  XC1          (4) 

Toluene  p-Chlor  toluene  p-Chlor  benzoic  acid 

The  ortho  compound,  while  obtained  in  small  amounts  by  the  above 
reaction,  is  better  prepared  from  the  ortho  amino  acid  by  the  diazo 
reaction  and  replacement  of  the  diazo  group  with  a  halogen  by  the 
Sandemeyer  reaction  or  by  means  of  potassium  iodide  (p.  598). 

COOH  (i)         diazo. 
C6H/ 

XNH2      (2)  tlze 

o-Amino  benzoic  acid 

COOH          (i)  COOH  (i) 

C6H/  +  K)-I  -  >        C6H/ 

XN2-(S04H  (2)  XI  (2) 

o-Carboxy  benzene  o-Iodo  benzoic  acid 

diazonium  sulphate 


NITRO   AND   AMINO   AROMATIC  ACIDS  705 

ortho-Iodo  Benzoic  Acid. — The  ortho-iodo  benzoic  acid  just  given 
in  the  last  synthesis  is  important  historically  because  it  was  the  first 
iodine  compound  to  yield  iodoso  and  iodoxy  derivatives  (p.  508)  as 
follows : 

/COOH  HNO3,HC1 

C6H4<  +0 

\j  acid  KMn04 

lodo  benzoic  acid 

/COOH  alkaline'  ,COOH 

CeH4\  -f-  O  »  CeH4\ 

XIO  KMnO4  \02 

Iodoso  benzoic  Iodoxy  benzoic 

acid  acid 

NITRO  AND  AMINO  AROMATIC  ACID^ 

Nitro  Benzoic  Acids. — The  nitro  ring-substituted  acids  are  not  in 
themselves  of  special  importance,  but  on  reduction  they  yield  the 
corresponding  amino  acids  which  have  many  important  members. 
The  two  groups  may  thus  be  considered  together.  When  direct  nitra- 
tion of  the  aromatic  acid  is  carried  out  by  treatment  with  nitric  acid 
or  a  mixture  of  nitric  and  sulphuric  acids  the  chief  product  is  the  meta 
compound.  In  the  case  of  benzoic  acid  the  yield  of  isomeric  products 
is  about  as  follows: 

/COOH  COOH  (i) 

C6H4<^  +~HO)— NO2       — >     C6H4<^ 

(H  XN02       (3) 

Benzoic  acid  m-Nitro  benzoic  acid  78  % 

COOH  (i)  /COOH  (i) 

C6H4<(  C6H/ 

XN02       (2)  N02       (4) 

o-Nitro  benzoic  p-Nitro  benzoic 

acid  20  %  acid  2  % 

Anthranilic  Acid. — Nitration  of  toluene  and  subsequent  oxidation 
yields  largely  the  para  and  ortho  compounds.  A  fact  of  interest  in 
connection  with  these  nitro  benzoic  acids  is  that  the  ortho  acid  is  sweet 
while  the  meta  and  para  acids  are  bitter.  On  reduction  with  tin  and 

45 


706  ORGANIC  CHEMISTRY 

hydrochloric  acid  the  nitro  benzoic  acids  yield  the  corresponding 
amino  benzoic  acids. 

COOH  (i)  COOH 

C6H/  +H    Sn_±*C      C6H/ 

XNO2       (2)  XNH2 

o-Nitro  benzoic  acid  o-Amino  benzoic  acid 

Anthranilic  acid 

The  ortho-amino  benzoic  acid  is  known  also  as  anthranilic  acid  and  is 
the  most  important  of  the  amino  benzoic  acids.  In  addition  to  the 
above  synthesis,  the  ortho-nitro  benzoic  acid  being  prepared  from 
ortho-nitre  toluene  by  oxidation,  the  amino  acid  may  also  be  made  by 
converting  the  ortho-nitro  toluene  into  ortho-amino  toluene  or  ortho- 
toluidine,  the  latter  being  also  a  natural  product  of  coal  tar  distillation 
and  a  constituent  of  crude  aniline  made  from  unpurified  benzene  through 
the  nitro  compound  (p.  544).  ortho-Toluidine  on  oxidation  yields  the 
anthranilic  acid. 

CH3  (i)  COOH  (i) 

C6H4<(  ±_X     C6H/ 

NNH2  (2)  XNH2  (2) 

o-Toluidine  Anthranilic  acid 

Relation  to  Indigo.  —  These  syntheses  while  establishing  the  con- 
stitution of  anthranilic  acid  as  ortho-amino  benzoic  acid  are  not  the 
most  important.  The  extreme  importance  of  this  particular  amino 
acid  is  in  its  connection  with  the  synthesis  of  the  valuable  dye  indigo. 
The  relation  of  the  acid  to  indigo  involves  several  other  compounds 
which  must  be  mentioned.  The  Portugese  name  for  indigo,  viz.,  anil, 
has  given  us  the  name  for  anil-ine  which,  as  stated  before  (p.  539),  is 
obtained  when  indigo  is  distilled  with  alkali.  It  also  gives  us  the  name 
anthr-anil-ic  acid,  for  this  acid  is  obtained  from  indigo  on  fusion  with 
alkali.  That  it  is  an  intermediate  product  in  the  breaking  down  of 
indigo  to  aniline  is  shown  by  the  fact  that  it  yields  aniline  by  the  loss 
of  carbon  dioxide  just  as  benzoic  acid  yields  benzene. 

X(COO)H     -CO2 
C6H/  --  '      C6H5—  NH2 

\  Aniline 


Anthranilic  acid 


NITRO  AND  AMINO  AROMATIC  ACIDS  ^07 

Isatin.  —  Another  compound  is  also  obtained  on  the  oxidation  of 
indigo,  viz.,  isatin.  That  isatin  is  related  to  anthranilic  acid  and  is 
probably  another  intermediate  product  of  the  breaking  down  of  indigo, 
lying  between  indigo  and  anthranilic  acid,  may  be  seen  by  the  follow- 
ing synthesis  of  isatin  from  ortho-nitro  benzoic  acid. 

,COOH  (i)     +PC15  ,COC1  (i)     +  KCN 


N02       (2)  NO2     (2) 

o-Nitro  benzoic  acid  o-Nitro   benzoyl 

chloride 


,CO—  CN  (i)     +H2O  ,CO—  COOH  (i) 

' 


NO2.          (2)  NO2  (2) 

Nitrile  o-Nitro  benzoyl  formic  acid 

.CO—  COOH  (i)  ,CO—  CO(OH)  (i) 


N02    .  (2)  NH(H  (2) 

o-Nitro  benzoyl  formic  o-Amino  benzoyl  formic 

acid  acid 

(I) 


\  / 

XCO      or      C6H/  C—  OH 

XNHX  X  N  ' 


(2)          Isatin 

>   '     (Taulomeric  forms) 

Anthranil.  —  The  same  characteristic  anhydride  linkage  between  the 
ortho  carboxyl  and  amino  groups  is  found  in  another  compound  that, 
because  of  its  relation  to  anthranilic  acid,  which  it  yields  by  addition 
of  water  when  heated  with  sodium  hydroxide  solution,  is  known  as 
anthranil.  It  is  related  to  anthranilic  acid  as  an  inner  anhydride. 

XCO(OH)     +H2O  /CO 

/  •*  --      r*  TT  /     I 

v  CeAl4v       I 

XNH(H)  XNH 

Anthranilic  acid  Anthranil 

Such  anhydride  relation  between  ortho  groups,  from  which  water  may 
be  lost,  has  been  found  before  in  the  cases  of  phthalic  anhydride  (p. 
689),  phthalimide  (p.  691),  and  succinic  anhydride  and  succinimide 
(p.  280-283). 


708  ORGANIC  CHEMISTRY 

Oxindole.  —  Still  one  more  related  compound  should  be  mentioned. 
This  is  oxindole  which  is  a  reduction  product  of  isatin. 

/CO,  /CH, 

C6H/         )CO    -  >     C6H/          )CO 
X  XX 


Isatin  Oxindole 

All  of  these  compounds  which  we  have  given  as  related  to  anthranilic 
acid  and  to  indigo  are  plainly  derivatives  of  ortho-ammo  aromatic 
acids,  either  benzoic  acid  itself,  as  in  anthranilic  acid  and  anthranil, 
or  side-chain-carboxy  acids,  as  in  isatin  and  oxindole. 

Synthesis  of  Anthranilic  Acid  and  Indigo.  —  While  anthranilic  acid 
was  first  obtained  from  indigo  the  importance  of  the  acid  now  is  due  to 
the  fact  that  it  is  an  intermediate  step  in  the  synthesis  of  indigo.  It  was 
through  a  study  of  the  relationships  which  we  have  just  been  discussing 
that  a  commercial  method  for  the  synthesis  or  this  valuable  dye  was 
worked  out.  Anthranilic  acid  may  be  converted  into  indigo  by  a  reac- 
tion which  we  shall  not  discuss  in  detail  until  indigo  itself  is  studied. 
To  make  such  a  synthesis  of  indigo  successful  it  was  necessary,  however, 
to  secure  other  methods  than  those  given  for  synthesizing  the  acid 
and  especially  to  have  as  the  starting  point  a  cheap  commercial 
compound. 

Synthesis  from  Phthalic  Acid  and  Naphthalene.  —  This  was  found 
when  anthranilic  acid  was  synthesized  from  ortho-phthalic  acid  which, 
as  has  been  stated,  may  in  turn  be  synthesized  from  naphthalene,  a 
cheap  abundant  compound.  The  conversion  of  naphthalene  into 
ortho-phthalic  acid  we  have  given  (p.  689)  as  resulting  from  chlorina- 
tion  and  subsequent  oxidation. 

.COOH  (i) 
C10H8  +  C1  +  0       -»     C6H/ 

th&e  XCOOH    (2) 

o-Phthalic  acid 

The  details  of  this  synthesis  will  be  explained  under  naphthalene 
(p.  766).  The  synthesis  of  anthranilic  acid  from  0r//w-phthalic  acid 
takes  place  according  to  the  following  reactions.  Phthalic  acid,  or 
better  phthalic  anhydride,  by  treatment  with  ammonia  yields  phthal- 
amidic  acid,  which  in  turn  yields  phthalimide. 


NITRO  AND  AMINO  AROMATIC  ACIDS  709 

COOH   (i)  XCO(OH)  (i) 

+H)—  NH2  -  -»  C6H/  -> 

CO(OH  (2)  XCO—  NH(H)  (2) 

o-Phthalic  acid  o-Phthalamidic  acid 

(i) 


H2O 


,co 

H/ 


(2) 

Phthalimide 


,.  ,  (i) 

C6H/     j  X0  +  H—  NH2       -*    C6H4 


CO—  NH(H)(2) 

Phthalic  anhydride 

The  reaction  is  accomplished  by  simply  heating  together  phthalic  anhy- 
dride and  ammonium  carbonate.  Phthalimide  then  hydrolyzes  with 
potassium  hydroxide  yielding  the  potassium  salt  of  phthalamidic  acid 
and  this  acid  amide  compound  undergoes  the  Hofmann  reaction  (pp. 
148,  685)  with  bromine  (or  chlorine)  and  potassium  hydroxide  by  which 
one  of  the  carboxyl  groups  is  replaced  by  the  amino  group  yielding 
amino  benzoic  acid  or  anthranilic  acid. 

co  'COOK 

C6H4<(       )>NH  +  KOH  —  >        C6H4<^ 

XCOX  XCO—  NH2 

Phthalimide  Potassium  phthalamidate 

Hofmann  Reaction.  —  In  the  reaction  with  phthalic  acid  or  anhy- 
dride and  ammonia  the  phthalamidic  acid  may  be  isolated  without  go- 
ing on  to  phthalimide.  In  this  case  the  action  of  potassium  hydroxide 
is  simply  neutralization  and  formation  of  the  above  salt.  The  Hof- 
mann reaction  with  phthalamidic  acid  may  be  represented  in  steps  as 
follows: 

COOK  (i)  /COOK      •    (i) 

C6H/  +  Br)—  Br       -  >       C6H4<( 

XCO—  NH)H  (2)  XCO—  NHBr  (2) 

Phthalamidic  acid  Bromide  of  phthalamidic  acid 

(salt)  (salt) 

.COOK  (i) 

C6H4(  +  K-(OH  — 

XCO—  N(H)Br  (2) 


710  ORGANIC  CHEMISTRY 

COOK          (i)  COOK       (i) 


C6H/  JE*lr       CeH/' 

XCO— NKBr(2)  XN  =  C  =  0  (2) 

o-Carboxy 
phenyl  iso-cyanate 

COOK          (i)  COOK   (i)  +HC1 

C6H4<(  +H20  ->         C6H4<^ 

XN=(C  =  0)(2)  NNH2      (2) 

Iso-cyanate  Potassium  anthranilate 

,COOH    (i) 


SNH2       (2) 

Anthranilic  acid 

Phenyl  Glycine  ortho-Carboxylic  Acid. — The  next  step  toward  in- 
digo is  the  formation  of  phenyl  glycine  ortho-carboxylic  acid  which  is  an 
ortho-ammo  derivative  of  a  mixed  ring-carboxy  and  side-chain-carboxy 
acid.  With  chlor  acetic  acid  anthranilic  acid  forms  an  amino  acetic 
acid  derivative  in  which  anthranilic  acid,  acting  as  ammonia  or  an 
amine,  is  substituted  in  acetic  acid. 

,COOH  COOH 

C6H/  +  Cl)— CH2— COOH  >  C6H4<( 

XNH)H  XNH— CH2— CCOH 

Anthranilic  acid  Phenyl  glycine  o-carboxylic  acid 

Anthranilo  acetic  acic 

This  compound  may  be  termed  anthranilo  acetic  acid,  but  as  it 
is  also  a  phenyl  substituted  glycine  or  amino  acetic  acid  it  is  termed 
phenyl  glycine  ortho-carboxylic  acid.  The  rest  of  the  synthesis  of 
indigo  will  be  discussed  under  indigo  itself,  but  as  it  all  involves  the 
original  synthesis  of  anthranilic  acid  from  a  cheap  raw  material  and 
as  the  phenyl  glycine  0r//?0-carboxylic  acid  is  an  amino  aromatic  acid, 
this  much  has  been  given  here. 

Methyl  Anthranilate. — The  methyl  ester  of  anthranilic  acid,  methyl 

COOCH3  (i) 
anthranilate,  C6H4^  ,  is  a  constituent  of  the  oil  of  orange 

XNH2  (2) 

blossoms  (Neroli  oil)  or  of  sweet  orange  peel  and  the  oil  of  Jasmin 
flowers.     It  is  valuable  as  a  perfume. 

Nitro  and  Amino  Cinnamic  Acids. — Two  other  nitro  aromatic  acids 
and  their  corresponding  amino  acids  should  be  mentioned  all  of  which 


NITRO  AND  AMINO  AROMATIC  ACIDS  71  1 

have  been  associated  with  the  development  of  the  synthesis  of  idigo. 
These  are  ortho-nitro  cinnamic  acid  and  ortho-amino  cinnamic  acid, 
which  are  side-chain-carboxy  acids  with  an  ethylene  unsaturated  or 
double  bond  group. 

CH  =  CH—  COOH  (i)  CH=CH—  COOH  (i) 

C6H/  C6H/ 

NO2  (2)  XNH2  (2) 

o-Nitro  cinnamic  acid  o-Amino  cinnamic  acid 

ortho-Amino  Phenyl  Propiolic  Acid.  —  The  corresponding  acetylene 
unsaturated  or  triple  bond  acid  is  phenyl  propiolic  acid.  The  nitro 
and  amino  derivatives  are 


£  =  C—  COOH  (i)  /C^C—COOH  (i) 


C6H4 

N02  (2)  NH2  (2) 

o-Nitro  phenyl  propiolic  acid  o-Amino  phenyl  propiolic  acid 

The  latter  pair  of  acids  may  be  formed  from  the  former  by  loss  of  hy- 
drogen bromide  from  the  side-chain  bromine  substitution  product. 

Phenyl  Alanine.  —  Phenyl  propionic  acid  yields  a  side-chain-sub- 
stituted amino  derivative  which  is  alpha-amino  beta-phenyl  propionic 
acid.  As  alpha-ammo  propionic  acid  is  known  as  alanine  this  phenyl 
derivative  is  named  phenyl  alanine. 

C6H5—  CH2—  CH(NH2)—  COOH 

Phenyl  alanine 

It  is  obtained  as  one  of  the  amino  acid  cleavage  products  of  the  hydrolysis 
of  proteins  (p.  389). 

Azo,  Hydrazo  and  Diazo  Acids.  —  From  the  nitro  aromatic  acids 
there  may  be  obtained  on  proper  reduction  of  the  nitro  group  (p.  537) 
the  corresponding  azo  and  hydrazo  compounds  which  bear  exactly  the 
same  relation  to  the  nitro  acids  and  amino  acids  that  the  simple  azo 
and  hydrazo  benzene  do  to  nitro  benzene  and  aniline.  Also  from  the 
amino  acids  by  diazotization  we  may  obtain  diazo  acids.  These  diazo 
acids  may  be  used  as  intermediate  products  in  preparing  other  sub- 
stituted acids  from  the  amino  acids  by  replacing  the  diazo  group  with 
other  groups  by  any  of  the  diazo  reactions  (p.  600).  Historically  the 
diazo-benzoic  acids  are  important  as  it  was  with  these  compounds  that 
Griess  first  carried  out  his  investigations. 


712  ORGANIC  CHEMISTRY 

SULPHO  AROMATIC  ACIDS 

The  sulpho  aromatic  acids  are  mixed  sulphonic  acid  and  carboxy 
acid  derivatives  of  the  hydrocarbons.  They  may  be  prepared  by  sul- 
phonating  the  aromatic  acid  directly  in  which  case  the  meta  product 
is  obtained.  To  prepare  the  ortho  or  para  compounds  a  hydrocarbon 
is  first  sulphonated  and  then  the  side  chain  is  oxidized  to  carboxy  1. 

Sulpho  Benzole  Acid.  —  When  toluene  is  sulphonated  with  concen- 
trated sulphuric  acid  a  mixture  of  ortho  and  para  toluene  sulphonic 
acid  is  obtained. 


(i) 
C6H4<  +HO)—  S02-OH       -»     C6H 

X(H  XS02OH(2),  (4) 

Toluene  o-,  p-Toluene  sulphonic  acids 

On  oxidation  of  these  compounds  the  products  are  the  corresponding 
sulpho  benzole  acids. 

CH3  COOH 

C6H/  +0       —  >    C6H4<( 

XSO2OH  XS02OH 

Toluene  sulphonic  acid  Sulpho  benzoic  acid 

Saccharin.  —  When  ortho-sulpho  benzoic  acid  is  treated  with  phos- 
phorus pentachloride  the  sulphonic  acid  group  yields  the  sulphon 
chloride  group  and  this  with  ammonia  yields  the  sulphamine  group. 

COOH          (i)  COOH        (i) 

C6H/  -»     C6H5<(  +H)-NH2  --  > 

XS02—  (OH     (2)  XS02—  (Cl     (2) 

o-Sulpho  benzoic  acid  o  -Benzoic  sulphon  chloride 

,COOH        (i) 
CeH/ 

XSO2—  NH2  (2) 

o-Sulphamine 
benzoic  acid 

Now  0r//f0-sulphamine  benzoic  acid  readily  loses  water  and  yields  an 
imide  anhydride. 

yCO(OH)  CO 

C6H/  -»     C6H/ 

XSO2—  NH(H)  XSO 

o-Sulphamine  benzoic  acid  o-Benzoic  sulphinid 

Saccharin 


SACCHARIN  713 

Saccharin  Synthesis.  —  This  anhydride,  or  ortho-benzoic  sulphinid, 
is  a  very  sweet  non-carbohydrate  substance  and  has  been  named 
saccharin.  It  is  about  three  hundred  times  as  sweet  as  cane  sugar.  In 
practice  the  reaction  is  carried  out  a  little  differently.  Toluene  is 
sulphonated  and  then  converted  into  the  corresponding  sulphon 
chlorides  which  will  be  a  mixture  of  the  ortho  and  para  compounds.  The 
toluene  is  still  better  converted  directly  into  the  mixed  ortho  and  para- 
toluene  sulphon  chlorides  by  treatment  with  suplhuryl  chloride,  SO2- 
C12.  The  mixed  sulphon  chlorides  are  then  separated  by  filtering  with 
ice,  the  para  compound  being  solid  while  the  ortho  is  a  thick  oily  liquid. 
The  pure  ortho-toluene  sulphon  chloride  is  then  treated  with  ammonia 
and  converted  into  the  ortho-toluene  sulphonamide.  The  ortho- 
toluene  sulphonamide  is  then  oxidized  with  alkaline  potassium  per- 
manganate to  the  potassium  salt  of  ortho-sulphamine  benzoic  acid. 
On  acidifying,  0r//?0-sulphamine  benzoic  acid  is  obtained  which  loses 
water  at  once  and  the  product  is  saccharin. 


(i)  +  PC15 

C6H  +  HO)—  S02—  OH  -  »C6H4< 

\K  XS02-(OH)(2),(4)         1 

Toluene  o-,  p-Toluene 

sulphonic  acid 


y3  X3  (i) 

C6H/          +C1)—  S02—  Cl  -  >  C6H4<( 

X(H  XS02C1  (2)  (4) 

o-,  p-Toluene 
sulphon  chloride 

XCH3         (i)  yCH3  (i) 

C6H/  +  H)—  NH2  -  >   C6H/ 

XSO2—  (Cl(2)  XSO2—  NH2  (2) 

o-Toluene  sulphon  chloride  o-Toluene  sulphonamide 

+  O  .COOK        (i) 

-»  C6H/  +HC1  -  -» 

(KOH+KMnO4)  SO2—  NH2  (2) 

o-Sulphamine 
benzoic  acid  (salt) 

(i) 

.CO(OH)         (i)  -H20  ,CO 

C6H4<  C6H4<f        > 

XS02—  NH(H)(2)  SO/ 

o-Sulphamine  (  ~\ 

benzoic  acid  .     \*'  . 

Saccharin 


714  ORGANIC  CHEMISTRY 

Saccharin  was  discovered  in  1879  by  Remsen  and  Fahlberg.  It  is 
only  slightly  soluble  in  cold  water,  but  is  soluble  in  hot  water,  acetone, 
alcohol  or  ether.  From  acetone  it  crystallizes  in  beautiful  crystals.  It 
is  a  valuable  medicinal  substance  as  it  can  be  used  for  its  sweetening 
effect  in  food,  by  persons  who  have  the  disease  known  as  diabetes  and 
who  are  unable  to  use  cane  sugar,  and  only  a  minimum  of  any  car- 
bohydrate food.  It  does  not  possess  any  nutritive  value,  however.  It 
is  also  used  as  a  food  preservative,  but  its  use  is  restricted  or  prohibited 
by  most  pure  food  laws.  It  is  interesting  that  only  the  ortho-sulph- 
amine  benzoic  acid  yields  such  a  sulphinid  anhydride.  The  para 
compound,  on  heating,  yields  other  products. 

HYDROXY  AROMATIC  ACIDS 
PHENOL  RING-CARBOXY  ACIDS 

/COOH  (i) 

Salicylic  Acid,  CeH^  ortho-Hydroxy  Benzoic  Acid 

XOH       (2) 

The  hydroxy  aromatic  acids  constitute  an  important  group.  They 
may  be  of  the  several  types  given  in  the  introductory  general  discus- 
sion, e.g. 

yCOOH 

Ring-hydroxy  ring-carboxy  acids,  C6H4<^  Salicylic  acid 

Phenol  acids  X)H 

<^H2— COOH 
Hydroxy  phenyl  acetic  acid 
H 
Phenol  side-chain  acids 

/COOH  meth 

Side-chain-hydro xy  ring-carboxy  acids.      CeH4\  ,          .       ' 

AI    u  i      -j  \^TT      ^TT          benzoic  acid 

Alcohol  acids  XCH2— OH 

Side-chain-hydroxy  side-chain-carboxy  acids,  CeHs— CH(OH)— COOH,      Phenyl 
Alcohol  side-chain  acids  hydroxy 

acetic  acid 

The  most  important  of  the  ring-hydroxy  acids  or  phenol  acids,  is  the 
ortho-hydroxy  benzoic  acid  commonly  known  as  salicylic  acid,  with 
the  formula  given  above.  We  may  use  this  and  the  isomeric  hydroxy 
benzoic  acids  (meta  and  para)  as  our  illustration  for  the  general  methods 
of  preparing  phenol  acids.  As  these  compounds  are  mixed  phenols 
and  aromatic  ring-carboxy  acids  two  general  methods  are  possible  for 
their  synthesis,  (i)  General  methods  for  preparing  phenols,  in  which 


HYDROXY   AROMATIC    ACIDS 


715 


case  we  start  with  ring-substituted  ring-carboxy  acids.  (2)  General 
methods  of  preparing  acids,  in  which  case  our  starting  point  will  be 
substituted  phenols  or  phenols  of  benzene  homologues. 

From  Sulpho  Benzole  Acid.  —  The  most  common  method  of  pre- 
paring phenols  is  by  the  alkali  fusion  of  the  sulphonic  acids.  Sulpho 
benzoic  acids  will  thus  yield  hydroxy  benzoic  acids.  In  case  the  sulpho 
benzoic  acid  has  been  made  by  direct  sulphonation  of  benzoic  acid  the 
meta  compound  will  result.  If,  however,  we  start  with  toluene  and 
sulphonate  it  we  will  obtain  the  ortho  and  para  compounds. 


4<( 
X 


COOH 


C6H 

X(H  +  HO)— SO2— OH 

Benzoic  acid 

.COOH       (i) 

/"»     TT    / 

\02— OH  (3) 

m-Sulpho  benzoic  acid 


CeH 


+  HO)—  SO2—  OH 


KOH 

—  r* 

fusi°n 


COOH(i) 


>H       (3) 

m-Hydroxy  benzoic  acid 

(i) 

,CH3 


, 
XS02—  OH 


Toluene 


o-,  p-Toluene 
sulphonic  acids 


d) 

COOH 


(i) 


x 
XSO2OH  fusion) 


o-,p-Sulpho 
benzoic  acids 


OH 


o-,  p-Hydroxy 
benzoic  acids 


From  Amino  Benzoic  Acid.  —  Amino  acids  by  the  diazo  reaction  and 
decomposition  with  water  will  yield  the  corresponding  phenol  acids. 
In  such  cases  also  if  we  start  with  benzoic  acid,  nitrate  directly  and 
reduce  this  to  the  amino  compound,  the  final  product  of  the  diazo 
reaction  will  be  the  meta  hydroxy  acid.  If  we  start  with  toluene  and 
nitrate  it  and  then  proceed  as  in  the  foregoing  and  oxidize  the  amino 
toluene  to  amino  benzoic  acid  our  product  will  be  the  ortho  and  para 
hydroxy  acids. 


7l6 


ORGANIC  CHEMISTRY 


/COOH 
C6H4< 

XH 

Benzoic  acid 


HO)—  N02 


COOH(i) 
C6H4<( 

N02     (3) 

m-Nitro  benzoic  acid 


diazo 


NH2     (3) 

m-Amino  benzoic  acid 


+  H 


4\ 


C6H 


/CH3 
/ 
N(H 

Toluene 


HO)—  N08 


reactons 

m-Hydroxy  benzoic  acid 

CH3  (i)  +H 


02(2),(4) 

o-,  p-Nitro  toluene 

diazo 


COOH  (i) 


4v  >          e 

XNH2(2),(4)   reactions  OH       (2),  (4) 

o-,  p-Amino  benzoic  acid  o-,  p-Hydroxy  benzoic  acids 

From   Phenol.  —  General   methods   for  preparing   acids   may   be 
applied  first  to  the  phenols  of  benzene  homologues.     Thus  by  the  oxi- 


dation  of  the  three  cresols,  hydroxy  toluenes,  C6H4 


/ 


CH 


we  should 


OH 


obtain  the  corresponding  hydroxy  acids.  An  interesting  fact,  however, 
is  that  the  presence  of  the  hydroxyl  group  in  the  ring  protects  the  methyl 
group  from  oxidation  and  we  cannot  thus  oxidize  the  cresols  as  indi- 
cated. If  we  convert  the  phenol  into  a  phenol  ether  or  a  phenol  ester, 
however,  the  oxidation  will  take  place,  the  ester  being  then  hydrolyzed 
to  the  acid. 


, 

C6H4<(  +0 

XO—  OC—  CH3 

o-,  m-,  p-Cresyl  acetate 


COOH 


/ 

4\ 

XO— 


_ 

'      2U 


OC—  CH3 

Phenol  ester  of  the  acids 


COOH 


OH 

o-,  m-,  p-  Hydroxy 
benzoic  acid 


This  method  is  not  often  used. 

Kolbe  Synthesis  from  Phenol  by  Carbon  Dioxide.  —  The  most  impor- 
tant method  of  synthesizing  the  phenol  acids  from  the  phenols  is  by 
an  interesting  reaction  known  as  the  Kolbe  synthesis,  and  especially 


HYDROXY    AROMATIC    ACIDS  717 

applicable  to  salicylic  acid.  It  consists  in  the  direct  introduction  of 
carbon  dioxide  into  the  benzene  ring  of  a  phenol  thus  producing  a 
carboxyl  group.  We  have  shown  that  formic  acid  is  the  reduction 
product  of  carbon  dioxide  (p.  135). 

H—  H  +  C02        -  >        H—  COOH 

Formic  acid 

Metallic  alkyls  yield  aliphatic  acids  with  carbon  dioxide. 
CH3—  Na  +  C02        -  >        CH3—  COONa 

Sodium  methyl  Acetic  acid  (salt) 

Also  mono-brom  benzene  and  sodium  yield  benzoic  acid  with  carbon 
dioxide. 

C6H5—  Br  +  Na2  +  CO2        -  >        C6H5—  COONa  +  NaBr 

Brom  benzene  %  Benzoic  acid  (salt) 

In  all  of  these  cases  the  carboxyl  group  results  from  the  direct  introduc- 
tion of  carbon  dioxide  in  front  of  a  hydrogen  or  sodium  atom.  Now  the 
sodium  compound  of  phenol,  viz.,  sodium  phenolate,  CeHs  —  ONa, 
undergoes  a  similar  reaction  yielding  first  a  phenyl  ester  of  carbonic 
acid  which  rearranges  into  salicylic  acid. 

rearrange- 
C6H5—  ONa  +  CO2        —  >     C6H6—  O—  CO—  ONa         —  > 

Sodium  phenolate  Phenyl  sodium  carbonate  , 

COONa     (i) 
CeH/ 

XOH  (2) 

Salicylic  acid  (salt) 

The  meta  and  para  hydroxy  acids  are  not  formed  by  this  reaction  but  if 
potassium  is  used  in  place  of  sodium  the  product  is  largely  the  para- 
hydroxy  acid. 

From  Phenols  by  CC14.  —  The  Reimer-Tiemann  reaction  for  the 
synthesis  of  hydroxy  aldehydes  (p.  659)  is: 

m  (+KOH)  XCHC12  (+HC1) 

+C1)—  CHC12     --  *     C6H/  +  2H2O 

OK 

Phenol  (salt)  OHO 


OK  Chloroform 


^ 

)H 

ydro 

zaldehyde 


o-,  (p-)  Hydroxy 
ben 


718  ORGANIC  CHEMISTRY 

The  principle  of  this  reaction  allows  the  synthesis  of  hydroxy  acids  if 
instead  of  chloroform  we  use  carbon  tetra-chloride,  CC14. 

(+KOH)  CC13  (+HC1) 

C6H  +C1)—  CC13         -*     C6H/ 


T'  Carbon 

K       tetra-chloride 

Phenol  (salt) 

COOH 
CeH/ 

X)H 

o-,  (p-)  Hydroxy 
benzoic  acid 

From  Phenol  Alcohols  and  Phenol  Aldehydes.  —  The  phenol  alcohols 
and  phenol  aldehydes  will  of  course  yield  phenol  acids  on  oxidation. 
Reactions  for  these  need  not  be  written  as  they  have  been  given  in 
general  at  various  times.  Salicylic  acid  or  ortho-hydroxy  benzoic  acid 
has  the  constitution  assigned  to  it  as  proven  by  the  syntheses  just 
discussed. 

Salicin.  —  It  derives  its  name  from  the  glucoside  salicin  which  is 
present  in  the  bark  of  willow  trees,  the  generic  name  of  which  is  Salix. 
When  the  glucoside  is  hydrolyzed  it  yields  glucose  and  a  compound 
known  as  saligenin,  which  is  salicylic  alcohol  or  ortho-hydroxy  benzyl 
alcohol)  and  which  on  oxidation  yields  salicylic  acid.  This  is  one  of  the 
natural  sources  of  the  acid. 

Oil  of  Wintergreen.  Methyl  Salicylate.  —  The  most  interesting 
natural  source  of  the  acid,  however,  is  oil  of  winter  green  obtained  from 
the  wintergreen  plant,  Gaultheria  procumbens.  The  chief  constituent 
of  this  oil  is  the  methyl  ester  of  salicylic  acid,  methyl  salicylate, 

3    x  .     On  boiling  the  oil  with  dilute  acids  the  salicylic 

acid  is  obtained.  Synthetic  oil  of  wintergreen  is  made  by  esterifying  sali- 
cylic acid  with  methyl  alcohol.  Salicylic  acid  is  a  white  crystalline  solid, 
m.p.  156°,  which  sublimes  on  heating  to  200°.  It  is  slightly  soluble  in 
cold  water,  i  part  in  444  parts,  but  easily  soluble  in  hot  water,  crystalliz- 
ing on  cooling  in  fine  needles.  It  gives  a  violet  color  reaction  with  ferric 
chloride  in  both  water  and  alcoholic  solutions  by  which  means  it  may 
be  distinguished  from  phenol  which  gives  the  color  reaction  in  water 
solutions  only.  With  bromine  it  is  precipitated  as  a  bromine  compound, 


HYDROXY  XROMATIC  ACIDS  719 

C6H3Br2  —  OBr.     When  heated  alone,  but  better  with  lime,  it  loses 
carbon  dioxide  and  yields  phenol. 

(COO)H  (-CO,) 

C6H4<(  +Ca(OH)2         —     C6H5—  OH 

XOH  pheno1 

Salicylic  acid 

Medicinal  Properties.  —  Salicylic  acid  is  an  antiseptic  and  preserva- 
tive, being  used  in  the  preservation  of  foods,  though  generally  restricted 
or  prohibited  by  pure  food  laws. 

Salol  and  Aspirin.  —  The  sodium  salt  and  several  derivatives  possess 
medicinal  properties  as  internal  antiseptics,  as  antipyretics  or  tempera- 
ture reducers,  and  to  lessen  the  pain  of  rheumatism.  The  most  common 
of  these  are  salol,  which  is  the  phenyl  ester  of  salicylic  acid,  as  an  acid, 
and  aspirin,  which  is  the  acetic  acid  ester  of  salicylic  acid,  as  a  phenol. 
COOC6H5  COOH 

C6H 


/ 
X 


'OH  NO— OC—  CH3 

Salol  Aspirin 

Phenyl  salicylate  Acetyl  salicylic  acid 

Salol  is  used  as  an  intestinal  antiseptic.  It  is  prepared  by  heating 
salicylic  acid  alone  to  160°  to  240°.  In  this  case  one  molecule  loses 
carbon  dioxide  yielding  phenol  which  then  esterifies  with  another  mole- 
cule of  the  acid  yielding  the  phenyl  ester. 

COO(H  HO),  (-H2O)  COOC6H5 

C6H/  +  )>C6H4          ->    C.H/ 

XOH  H(OOCy  (-CO,)  XOH 

Salicylic  acid  Phenyl  salicylate,  Salol 

The  reaction  is  accomplished  better  by  heating  to  120°,  two  molecules 
of  salicylic  acid,  two  molecules  of  phenol  (or  sodium  phenolate)  and  one 
molecule  of  phosphorus  oxychloride,  POC13,  the  reaction  here  being 
the  same  as  the  second  step  in  the  preceding  one.  Aspirin  is  prepared 
by  acetylating  salicylic  acid  with  acetyl  chloride  in  the  presence  of 
acetic  anhydride,  sulphuric  acid,  zinc  chloride  or  sodium  acetate.  It 
also  is  an .  antipyretic  and" antiseptic.  Other  similar  derivatives,  e.g. 
betol,  containing  naphthol  and  quinoline  groups,  are  also  medicinal 
compounds  of  importance.  The  medicinal  action  of  these  salicylic 
esters  is,  that  in  the  intestine  they  become  hydrolyzed  and  yield 
salicylic  acid  or  sodium  salicylate,  which  then  acts  as  an  antiseptic  and 
antipyretic.  The  action  of  these  esters  is  less  violent  than  that  of 


720  ORGANIC  CHEMISTRY 

sodium  salicylate  itself  when  taken  internally  because  with  them  the 
salicylic  acid  is  liberated  slowly. 

Anisic  Acid. — A  derivative  of  para-hydroxy  benzoic  acid  is  the 

COOH  (i) 
methyl  ether,  CeH^  ,  known  as  anisic  acid.     It  is  related 

XOCH3    (4) 

to  anethole  and  anis  aldehyde  (p.  66 1),  and  like  them  occurs  in  oil 
of  anis  seed.  On  heating  it  loses  carbon  dioxide  and  yields  anisole, 
methyl  phenyl  ether. 

CH  =  CH— CH3  /CHO  (COO)H 

C6H/  C6H4<(  C6H/ 

XOCH3  X)CH3  XOCH3 

Anethole  Anis  aldehyde  Anisic  acid 

(Z^°2)         C6H6-OCH3 

Anisole 

POLY-HYDROXY  MONO-RING-CARBOXY  ACIDS 

When  more  than  one  hydroxyl  group  is  substituted  in  the  ring  of  an 
aromatic  acid  ther.e  will  result  poly-phenol  acids,  i.e.,  poly-hydroxy  acids. 
The  poly-hydroxy  benzoic  acids,  which  include  the  most  important 
members,  bear  the  same  relation  to  benzoic  acid  that  the  ordinary 
poly-phenols,  e.g.,  pyrocatechinol,  resorcinol,  pyrogallol,  etc.  (p.  617), 
do  to  benzene.  They  may  also  be  considered  as  carboxyl  substitution 
products  of  the  poly-phenols. 

Protocatechuic  Acid. — One  of  the  di-hydroxy  benzoic  acids  is  related 
to  vanillin,  which  we  have  already  studied.  The  acid  is  known  as 
protocatechuic  acid,  and  derives  its  name  from  the  fact  that  it  may  be 
obtained  from  a  gum  or  resin,  known  as  gum  catechin,  by  fusion  with 
potash,  i.e.  by  heat  and  oxidation  in  presence  of  an  alkali.  A  large 
variety  of  plant  products  including  alkaloids,  essential  oils,  gums,  resins 
and  tannins  yield  this  acid.  The  following  may  be  mentioned:  gum 
catechin,  gum  benzoin,  guaiac  resin,  myrrh,  piperine  or  piperic  acid, 
vanillin,  cajfe-tannic  acid.  These  natural  sources  at  once  suggest  a 
relationship  to  vanillin  (p.  661)  and  heliotropin  (p.  662).  It  is  the  acid 
corresponding  to  protocatechuic  aldehyde,  3 -4 -di-hydroxy  benzal- 
dehyde  (p.  66 1),  which  explains  the  relationship  just  mentioned.  Its 
constitution,  is  then: 


HYDROXY    AROMATIC   ACIDS 
COOH 


721 


o, 

Hi 

Protocatechuic  acid 
i-Carboxy  3-4-di-hydroxy  benzene 

Synthesis  from  meta-  or  para-Hydroxy  Benzoic  Acid. — The  con- 
stitution is  proven  by  its  synthesis  by  sulphonation  and  then  alkali 
fusion  of  either  meta-hydroxy  benzoic  acid  or  para-hydroxy  benzoic 
acid.  As  this  synthesis  introduces  into  each  of  these  acids  first  a 
sulphonic  acid  group  and  then  in  place  of  this  a  second  hydroxyl  group 
the  two  hydroxyls  in  the  final  product,  protocatechuic  acid,  must  be 
in  the  3-4  positions  as  only  such  positions  could  be  occupied  in  a  prod- 
uct obtained  from  either  the  meta  or  para  hydroxy  benzoic  acid, 


COOH 


COOH 


(H  -f  HO)— SO2OH 

m-Hydroxy  benzoic  acid 


OH 

(SO2OH  +  K)— OH 
COOH 


COOH 


fusion 


COOH 


OH 

Protocatechuic  acid 


(H  +  HO)— SO2OH 


O 
H 

p  -Hydroxy  benzoic  acid 

46 


(SO2OH+  K)— OH 


722  ORGANIC  CHEMISTRY 

This  proof  is  exactly  analogous  to  that  for  the  constitution  of  pseudo- 
cumene,  1-3 -4 -tri -methyl  benzene  from  either  meta-xylene  or  para- 
xylene  (p.  490).  That  the  two  hydroxyls  are  ortho  to  each  other  is 
proven  by  the  fact  that  on  heating  with  lime  protocatechuic  acid  yields 
pyrocatechinol,  i-2-di-hydroxy  benzene. 

(COO)H 

-C02 

+  C02 


Protocatechuic  acid 

This  relationship  explains  the  similarity  of  the  names  and  the  fact  that 
both  are  obtained  from  gum  catechin.  The  reverse  of  the  above  re- 
action, the  synthesis  of  protocatechuic  acid  from  pyrocatechinol,  may  be 
accomplished  by  heating  the  phenol  with  ammonium  carbonate  and 
water  to  1400°  under  pressure,  which  is  a  modification  of  the  Kolbe 
reaction  for  synthesizing  salicyclic  acid  (p.  716).  From  its  constitution 
and  by  reference  to  the  formulas  on  page  662  we  will  see  its  relationship 
to  vanillin,  heliotropin,  eugenole,  safrole,  guaiacol,  etc. 

Vanillic  Acid. — The  mono-methyl  ether  with  the  methoxy  group  in  the 
^-position  is  known  as  vanillic  acid,  as  it  is  the  acid  corresponding  to 
the  aldehyde  vanillin. 

CHO  COOH 


OCH3  k  JOCH 

\x 

o 

H 

Vanillic  acid 

Gallic  Acid. — The  3-4-5-tri-hydroxy  benzole  acid  is  known  as 
gallic  acid.  The  proofs  of  this  constitution  are  (i)  that  on  heating 
with  lime  and  the  loss  of  carbon  dioxide  we  obtain  pyrogallol  which  has 
been  proven  to  have  the  constitution  i-2-3-tri-hydroxy  benzene  (p. 
619);  and  (2)  that  it  may  be  synthesized  from  either  brom-protocate- 


HYDROXY    AROMATIC    ACIDS 


723 


chuic  acid  in  which  the  two  hydroxyls  are  in  the  3-4-positions  or  from 
brom  3-5-di-hydroxy  benzole  acid.  Therefore  the  three  hydroxyls  in 
gallic  acid  must  be  in  the  3-4-5-positions. 

(COO)H 


(— co8) 


Gallic  acid 


COOH 


COOH 


OH 


OH 


i-2-3-Tri 


HO 


acid 


Gallic  acid 


3-5-Di-hydrojcy 
benzoic  acid 


Gallic  acid  is  found  free  or  as  a  glucoside,  from  which  it  is  set  free  on 
hydrolysis,  in  several  plants,  e.g.  sumach,  gall  nuts,  acorns,  Chinese 
tea,  Dim-dim,  etc.  It  is  also  formed  by  the  acid  hydrolysis  of  tannins 
which  occur  in  these  or  similar  plants  which  possess  astringent  proper- 
ties. With  ferric  chloride  solution  gallic  acid  throws  down  a  blue- 
black  precipitate  which  is  soluble  in  excess  of  the  ferric  chloride  giving 
a  green  solution. 

Tannic  Acids. — Closely  related  to  gallic  acid  and  to  protocatechuic 
acid  is  a  group  of  acids  known  as  tannic  acids.  While  the  exact  con- 
stitution of  these  is  not  known  it  is  probable  that  they  are  anhydrides 
of  different  hydroxy  benzoic  acids,  similar  to  the  di-saccharoses  as  an- 
hydrides of  mono-saccharoses.  This  is  indicated  by  the  fact  that  on 
hydrolysis  the  tannic  acids  yield  hydroxy  benzoic  acids.  The  different 
tannic  acids  are  given  names  that  indicate  the  hydrolytic  products  or 
the  natural  source. 

Gallo-tannic  Acid. — One  of  these  is  gallo-tannic  acid,  also  known  as 
simply  tannic  acid,  or  tannin,  also  as  di-gallic  acid.  It  is  found  in  gall- 
nuts  and  in  tea  and  yields  gallic  acid  on  hydrolysis. 


724  ORGANIC  CHEMISTRY 

COOH    (l) 

Ci4H1009     +     H20  -- >        2C6H2/ 

Gallo-tannicacid  ^(OH),  (3-4-5) 

Gallic  acid 

Catechu-tannic  Acid. — A  tannic  acid  which  is  found  in  gum  cafe- 
chin  and  which  yields  catechin,  protocatechuic  acid  and  pyrocatechinol 
is  known  as  catechu-tannic  acid. 

Querci-tannic  Acid. — Another  tannic  acid,  probably  also  a  catechu- 
tannic  acid,  as  it  yields  the  same  products  as  above,  is  known  as  querci- 
tannic  acid.  It  derives  this  name  from  Quercus,  the  generic  name  for  the 
oak  tree,  as  it  is  found  in  oak  bark,  but  not,  however,  in  oak  galls. 

Caffe-tannic  Acid. — Another  tannic  acid  is  found  in  coffee  berries 
and,  therefore,  is  called  caffe-tannic  acid.  It  differs  from  the  other 
tannic  acids  in  not  precipitating  gelatin  and  can  not  be  used  in  tanning 
hides.  It  is  possibly  simply  a  coloring  substance  like  the  yellow  color- 
ing matter  of  gum  fustic,  fustian  yellow  or  maclurin.  It  is  sometimes 
termed  a  pseudo-tannin. 

Tannins. — It  has  just  been  stated  that  the  tannic  acids  are  probably 
anhydrides  of  poly-hydroxy  benzoic  acids,  especially  protocatechuic  acid 
and  gallic  acid.  Also  while  gallic  acid  is  found  free  in  gall-nuts  and 
certain  astringent  plants  it  is  probably  formed  by  the  hydrolysis  of 
glucosides  in  the  plant.  The  glucoside  mother  substances  of  the 
tannic  acids  are  known  as  tannins.  Recent  work  of  Fischer  has  shown 
that  tannin  is  undoubtedly  a  glucoside  of  five  molecules  of  di-gallic 
acid  or  gallotannic  acid,  and  one  molecule  of  glucose.  The  term  tannin, 
while  ordinarily  used  as  synonymous  with  tannic  acid,  is  more  correctly 
a  class  name  for  a  group  of  astringent  plant  products  which  possess 
certain  general  characters.  Some  of  the  characteristics  of  tannins  are 
as  follows:  (i)  They  are  astringent  colloidal  substances.  (2)  They 
precipitate  gelatin  and  form  insoluble  products  with  gelatin-yielding 
substances  such  as  animal  skins.  This  is  the  property  which  makes 
them  useful  in  tanning  hides  into  leather.  This  property  is  not  pos- 
sessed by  caffe-tannic  acid,  which  is  the  reason  for  considering  it  more 
truly  a  coloring  matter  or  a  pseudo-tannin.  (3)  With  ferric  chloride 
they  produce  a  blue-black  or  a  green  color.  This  property  is  utilized 
in  the  manufacture  of  iron  inks. 

Tannins  occur  quite  widely  distributed  in  the  plant  kingdom  giving 
to  the  plant  characteristic  astringent  properties.  The  most  common 


HYDROXY  AROMATIC  ACIDS  725 

sources  of  tannins  are  the  gall-nuts  formed  by  insects  on  various  plants 
such  as  oak,  tamarix,  etc.;  the  bark  and  wood  of  oak,  chestnut,  pine, 
acacia,  hemlock,  eucalyptus,  etc.;  the  leaves  of  sumach  and  the  roots 
of  canaigre.  The  different  tannins  have  been  classified  by  Procter  into 
two  divisions  similar  to  those  given  for  the  classification  of  the  tannic 
acids. 

1.  Pyrogallic   acid  tannins  which  yield   tannic  acids  convertible 
into  gallic  and  pyrogallic  acids.     These  tannins  give  a  blue-black  color 
with  ferric  chloride  and  give  no  precipitate  with  bromine  water.     They 
also  form  a  bloom  on  the  leather  from  hides  which  have  been  treated 
with  them.     These  include  tannins  of  gall-nuts,  sumach,  oak  and  chest- 
nut wood. 

2.  Pyrocatechinol  tannins  which  yield  tannic  acids  convertible  into 
protocatechuic  acid  and  pyrocatechinol.     These  tannins  give  a  green- 
black  color  with  ferric  chloride  and  yield  a  precipitate  with  bromine 
water.     They  do  not  produce  a  bloom  on  leather  in  tanning,  but  yield 
a  red  color  to  it.     These  include  tannins  of  oak  bark,  pine  bark,  acacia, 
canaigre,  etc. 

Tanning. — The  chief  use  of  the  tannins  is  in  the  process  known  as 
tanning.  Due  to  the  property  of  precipitating  gelatin  they  form  an 
insoluble  material  in  the  pores  of  gelatin-yielding  substances,  such  as 
animal  skins,  and  thereby  convert  the  skin  into  a  product  known  as 
leather.  This  property,  it  will  be  recalled,  is  not  possessed  by  the 
tannic  acid  found  in  coffee  beans.  The  use  of  tannins  for  the  process 
of  tanning  is  not  so  universal  as  formerly  owing  to  the  discovery  that 
similar  results  can  be  obtained  by  the  use  of  chromic  acid.  Leathers 
produced  by  tanning  with  chromic  acid  are  usually  cheaper  and  do  not 
seem  to  be  so  impervious  to  water,  though  the  wearing  quality  seems  to 
be  as  good  as  that  produced  by  oak  bark  tannin.  Tannins  are  also  used 
as  mordants  in  dyeing. 

Inks. — Formerly  all  writing  inks  except  so-called  India  ink,  which 
is  a  carbon  product,  were  made  by  the  treatment  of  ferric  salts  with 
tannin  or  tannic  acid.  The  green  solution  produced  with  excess  of 
the  iron  salt  becomes  black  on  drying  and  exposure  to  the  air.  Such 
iron  inks  may  be  bleached  by  means  of  oxalic  acid  which  reduces  the 
colored  ferric  compound,  produced  with  the  gallotannic  acid,  to  a 
colorless  compound.  At  the  present  time  many  writing  inks  are  made 
from  aniline  dyes.  These  are  not  bleached  with  oxalic  acid,  but  are 


726  OBGANIC  CHEMISTRY 

completely  decolorized  by  chlorine  or  by  Javelle  water,  which  is  a  solu- 
tion of  sodium  hypochlorite  made  from  bleaching  powder,  crude  calcium 
hypochlorite,  by  precipitating  the  calcium  with  sodium  carbonate  and 
filtering. 

PHENOL  SIDE-CHAIN  CARBOXY  ACIDS 

The  side-chain  carboxy  acids  which  we  have  studied  are  phenyl 
acetic,  phenyl  propionic  or  hydrocinnamic,  phenyl  acrylic  or  cinnamic 
and  phenyl  propiolic.  Phenol  derivatives  of  all  of  these  are  known. 
Hydroxy  phenyl  acetic  acid  is  not  important. 

Tyrosine. — para-Hydroxy-phenyl  propionic  acid  has  a  side-chain 
amino  derivative  which  is  one  of  the  amino  acid  cleavage  products 
obtained  by  hydrolyzing  proteins.  It  is  known  as  tyrosine. 

CH2— CH(NH2)— COOH    (i) 
C6H/ 

OH        (4) 

Tyrosine 
«- Amino  £- (para -hydroxy -phenyl)  propionic  acid 

This  compound  has  been  discussed  in  connection  with  the  aliphatic 
amino  acids  (p.  389),  as  its  relation  to  these  simpler  compounds  and  to 
proteins  is  more  important  than  its  relation  to  the  hydroxy  aromatic 
acids. 

Hydroxy  Cinnamic  Acid. — Cinnamic  acid  or  phenyl  acrylic  acid 
yields  ring  hydroxy  derivatives  of  which  the  ortho  compound  is  the 
important  one. 

Coumaric  and  Coumarinic  Acids. — Like  cinnamic  acid  it  exists  in 
geometric  stereo-isomeric  forms,  the  trans  form  being  known  as  cou- 
maric  acid  and  the  cis  form  as  coumarinic  acid. 

(2)  HO— C6H4— C— H  (2)     HO— C6H4— C— H 

II  II- 

HOOC— C— H  H— C— COOH 

Coumarinic  acid  Coumaric  acid 

cis  trans 

These  acids  are  readily  transformed  into  each  other.  As  in  the  case  of 
maleic  acid  and  fumaric  acid,  the  cis  form  easily  yields  an  anhydride 
while  the  trans  form  does  not.  In  fact  coumarinic  acid,  the  cis  com- 
pound, is  known  only  as  the  anhydride,  called  coumarin. 


HYDROXY  AROMATIC  ACIDS  727 

(l) 

(2)  (HO)-C6H4-C-H  _H,0      /CeH4-C-H  CH  =  CH 


(H)OOC— C— H  X)C C— H  NO CO 

Coumarinic  acid  /    \ 

Coumarin 

Coumarin.  New -mown  Hay. — Coumarin  is  a  pleasant  smelling 
compound,  and  is  the  odoriferous  constituent  of  the  plant  Asperula 
odorata  or  wood  ruff,  and  also  of  new-mown  hay.  It  is  also  present  in 
Tonka  beans  the  extract  of  which  is  used  as  a  substitute  for  vanilla. 

Perkin  Synthesis  of  Coumarin. — Coumaric  acid  and  coumarin  may 
be  synthesized  by  the  Perkin  reaction  for  synthesizing  unsaturated 
aromatic  acids  (p.  698).  These  syntheses  are  of  historical  interest  as 
the  two  compounds  obtained  were  the  first  ones  prepared  by  this  reaction. 
Instead  of  taking  a  simple  aromatic  aldehyde  it  is  only  necessary  to 
take  a  phenol  aldehyde,  viz.,  salicylic  aldehyde, 

(2)  HO— C6H4— CH  =  O  +  H—CH2— COONa        > 

Salicylic  aldehyde  Sodium  acetate 

-H20 
(2)  HO— C6H4— CH(OH)— (H)CH—  COONa 

Intermediate  product 

(2)  HO— C6H4— CH  =  CH— COONa 

Coumaric  acid 

(salt) 

The  salicylic  aldehyde  is  heated  with  sodium  acetate  and  acetic  an- 
hydride when  the  above  reaction  takes  place.  The  coumaric  acid 
obtained  as  the  sodium  salt  is  then  converted  into  its  acetyl  derivative. 
This  goes  over  to  the  isomeric  cis  form  and  by  the  loss  of  sodium  acetate 
yields  the  anhydride  coumarin. 

HO— C6H4— C— H  CH3— CO— O— C6H4— C— H 

!!  — >  II  — » 

H—C— COONa  H—C— COONa 

Coumaric  acid  Acetyl  coumaric  acid 

(salt) 


(CH3— CO— O)— C6H4— C— H  C6H4— C— H 

(Na)OOC— C— H  *  OC— C— H 

Acetyl  coumarinic  acid  Coumarin 

(salt) 


728  ORGANIC  CHEMISTRY 

If  we  examine  model  formulas  of  coumarinic  acid  and  coumarin  we  will 
see  that  the  former  is  really  a  delta-hydroxy  acid  and  the  latter,  there- 
fore, is  a  delta  lactone  (p.  243). 

ALCOHOL  ACIDS 

The  hydroxy  aromatic  acids  in  which  the  hydroxyl  is  in  the  side- 
chain  are  alcohol-acid  compounds.  They  therefore  possess  characters 
of  both  alcohols  and  acids.  They  may  also  be  of  the  two  types  with 

CH2OH 
the  carboxyl  in  the  ring,  e.g.,  CeH4<^  ,  hydroxy-methyl  benzoic 

XCOOH 

acid,  or  with  the  carboxyl  in  the  side-chain,  e.g.,  CeH5 — CH(OH)— 
COOH,  phenyl  glycolic  acid.  The  former  type  will  be  prepared  by 
methods  characteristic  of  aromatic  alcohols  and  ring  carboxy  acids, 
the  latter  by  those  for  side-chain-acids  and  alcohols. 

Hydroxy-methyl  Benzoic  Acid. — The  first  example  given  above  is 
important  in  connection  with  the  constitution  of  phthalide  (p.  693) 
and  phthalyl  chloride  (p.  692).  By  the  addition  of  water  phthalide  is 
converted  into  o -hydroxy -methyl  benzoic  acid. 

d) 
/CH2  CH2— OH(i) 

CeH4\  /O  +  H2O     >     CeH4v 

X  C(T  XCOOH       (2) 

(2) 

Phthalide  o -Hydroxy -methyl  benzoic  acid 

This  reaction  establishes  the  constitution  of  phthalide  as  a  lactone  not  a 
di-aldehyde  and,  therefore,  phthalyl  chloride  has  the  unsymmetrical 

CCk 
formula  C6H4<f  >O. 


Mandellic  Acid. — Mandellic  acid  is  phenyl  glycolic  acid, 
CH(OH) — COOH,  phenyl  hydroxy  acetic  acid.  This  constitution  is 
proven  by  its  synthesis  from  benzaldehyde  by  condensation  with 
hydrogen  cyanide  and  the  hydrolysis  of  the  resulting  nitrile. 


HYDROXY    AROMATIC    ACIDS  729 

H 

C6H5— C  =  O  +  H— CN > 

Benzaldehyde 

H 

I 
C6H5— C— OH  +  H2O     >     C6H5— CH(OH)— COOH 

Mandellic  acid 

CN 

Mandellic  nitrile 

Mandellic  acid  is  the  phenyl  analogue  of  lactic  acid  (p.  246). 

CH3— CH(OH)— COOH,  Lactic  acid 
C6H5— CH(OH)— COOH,  Mandellic  acid 

Like  lactic  acid  it  contains  an  asymmetric  carbon  atom  and  exists  as 
optically  active  stereo-isomers.  The  acid  synthesized  as  above  is  the 
optically  inactive  variety*  while  the  acid  obtained  from  amygdalin 
(see  below)  is  lew  rotatory.  The  inactive  form  may  be  split  into  its 
optical  components  through  the  cinchonine  salts  (p.  308).  The 
relationship  of  the  acid  to  benzaldehyde  explains  the  fact  that  the  two 
compounds  may  be  obtained  from  the  same  glucoside,  viz.,  amygdalin. 
This  glucoside,  it  will  be  recalled  (p.  654),hydrolyzes  naturally  by  means 
of  the  enzyme  emulsin,  or  by  means  of  acids,  into  glucose,  benzaldehyde 
and  hydrogen  cyanide.  When  amygdalin,  therefore,  is  boiled  with 
hydrochloric  acid  the  synthetic  reaction  given  above  takes  place  and 
mandellic  acid  is  obtained.  Amygdalin  is  present  in  the  oil  of  bitter 
almonds  the  botanical  name  of  which  is  Prunus  amygdalus.  Mandellic 
acid  gets  its  name  from  the  German  word  for  almond,  viz.,  Mandel. 


2.  DI-PHENYL  AND  RELATED  COMPOUNDS 
Di-phenyl,  C6H5— C6H5 


As  aromatic  compounds  we  have  thus  far  considered  representative 
members  of  all  of  the  important  classes  and  sub-classes  which  have  been 
derived  from  benzene  or  its  homologues.  The  homologues  include 
higher  hydrocarbons  which  result  from  the  substitution  of  one  or  more 
aliphatic  radicals,  either  saturated  or  unsaturated,  into  a  single  benzene 
ring.  Thus  in  the  hydrocarbons  of  the  benzene  series  proper  there  is 
only  one  benzene  ring.  There  are  other  hydrocarbons,  however,  which 
are  related  to  benzene  but  which  are  not  simple  homologues  as  above 
denned.  They  belong  to  a  new  and  distinctly  different  series.  The 
characteristic  of  the  series  of  hydrocarbons  which  we  shall  now  study 
is  that  they  consist  of  two  or  more  benzene  rings  which  are  linked  to 
each  other  either  directly  or  by  an  intervening  aliphatic  carbon  group. 

In  synthesizing  both  the  aliphatic  and  aromatic  hydrocarbons  we 
made  use  of  the  Wurtz,  Frankland,  Fittig  and  Friedel-Craft  reactions 
for  introducing  an  aliphatic  radical  in  place  of  hydrogen  of  the  original 
hydrocarbon,  thereby  forming  a  higher  member  of  the  homologous 
series. 

Wurtz  CH3— (I  +  Na2  +  I)~ CH3    >     CH3— CH3  +  2NaI 

Methyl  iodide  Methyl  iodide  Ethane  or  Di-methyl 

Frankland     C2H6— (I+Zn  +  I)— CH3  >  CH3— CH2— CH3  +  ZnI2 

Ethyl  iodide  Methyl  iodide  Propane 

Fittig  C6H5— (Cl  +  Zn  +  Cl)— CH3  — +  C6H5— CH3  +  ZnCl2 

Phenyl  chloride  Methyl  chloride  Toluene 

Friedel-        C6H6— (H  +  Cl)— CH3  (+ A1C13)     >    C6H6— CH3 

Craft  Benzene  Methyl  chloride  Toluene 

Di-phenyl. — If,  however,  instead  of  two  aliphatic  halides,  or  a  benzene 
halide  and  an  aliphatic,  we  use  the  benzene  halide  only,  the  same  kind 
of  reaction  takes  place  with  the  formation  of  a  hydrocarbon  of  the  com- 
position Ci2Hio.  Just  as  ethane  is  di-methyl  so  this  compound  must 
be  di-phenyl. 

C6H6—  (Br  +  Na2  +  Br)— C6H6       — >     C6HB— C6H5  +  2NaI 

730 


DI-PHENYL  AND  RELATED  COMPOUNDS  73! 

H        H                                                                H       H 
C C  C C 

HC/  V—  (Br  +  Na2  +  Br)— C/  \CH 

C        C 
H        H 

Phenyl  bromide 


C        C 

H       H 

Phenyl  bromide 

H      H 

H 

H 

C       C 

C 

C 

HC/  /C~~C\  /CH 

C       C  C       C 

H       H  H      H 

Di-phenyl 

From  Benzene. — It  is  possible  to  synthesize  di-phenyl  from  benzene 
directly  by  a  reaction  that  does  not  take  place  with  aliphatic  hydro- 
carbons. When  the  vapor  of  benzene  is  passed  through  a  red  hot  tube 
di-phenyl  is  obtained,  two  atoms  of  hydrogen  being  lost. 

-2H 
2C&H.Q          >         CeHs — CeHs 

Benzene        red  hot  tube  Di-phenyl 

Di-nitro  Di-phenyl. — Di-phenyl  is  present  in  the  distillation  prod- 
ucts of  coal  tar  probably  resulting  from  the  preceding  reaction.  It 
is  a  solid,  crystalline  compound;  m.p.  71°,  b.p.  254°.  It  acts  like  ben- 
zene in  yielding  halogen,  nitro  and  sulphonic  acid  products  by  the  direct 
action  of  halogens,  nitric  acid  or  sulphuric  acid,  In  cases  of  direct 
substitution,  when  two  groups  enter  the  compound  one  enters  each 
ring  in  the  positions  para  to  the  linking  carbon  atoms.  The  p-p-di- 
nitro  di-phenyl  may  also  be  prepared  by  heating  p-brom  nitro  benzene 
with  copper. 

(4)  02N—  C6H4— (Br  -f-  Cu  +  Br)— C6H4— NO2(4)     > 

i-Brom  4-nitro  benzene 

(4)  02N— C6H4— C6H4— N02    (4) 

4-4-Di-nitro  di-phenyl 


732 


ORGANIC  CHEMISTRY 


Benzidine. — This  4-4-di-nitro  di-phenyl  by  reduction  yields  the 
corresponding  4-4-di-amino  di-phenyl. 


02N— 


+  H 


>— NO2 


4-4-Di-nitro  di-phenyl 


-GO 

4-4-Di-aminp  di-phenyl 


Benzidine 


This  4^4-di-amino  di-phenyl  is  benzidine  which  yields  a  very  impor- 
tant group  of  dyes  and  which  is  formed  by  a  molecular  rearrangement 
from  hydrazo  benzene  (p. 


— NH— NH- 


Hydrazo  benzene 


rearrangement 


H2N 


-NH: 


Benzidine 


The  diazotization  of  benzidine  yielding  diazo  and  tetrazo  compounds, 
the  coupling  of  these  with  phenols  and  amines  yielding  azo  compounds, 
which  are  the  benzidine  dyes,  should  be  recalled  here  (p.  569). 

Di-anisidine. — A  derivative  of  di-phenyl  which  is  related  to  benzi- 
dine, and  related  also  to  anisole,  C6H5 — OCH3  (p.  612)  and  to  anisi- 
dine,  H2N — C6H4 — OCH3,  is  known  as  di-anisidine. 


H,N- 


— NH2    Di-anisidine 


OCH, 


OCH< 


This  also  yields  dyes  of  the  benzidine  class,  an  important  one  being 
benzo  sky  blue. 


DI-PHENYL  AND  RELATED  COMP  OUNDS  733 

Di-phenic  Acid.— A  di-carboxy  acid  of  di-phenyl  in  which  the  two 
carboxyls  are  both  ortho  to  the  ring  linkage  is  of  importance  in  connec- 
tion with  the  constitution  of  another  hydrocarbon,  phenanthrene, 
which  will  be  studied  later  (p.  806).  It  is  known  as  di-phenic  acid. 


Di-phenic  acid 


HOOC  COOH 


Di-phenyl  Methane,  C6H5— CH2— C6H6 

When  phenyl  chloride  and  benzyl  chloride  are  treated  with  sodium 
the  same  kind  of  reaction  takes  place  as  in  the  formation  of  di-phenyl 
and  a  compound  is  obtained  as  follows: 


-CH2— (Cl  +  Na2  +  Cl)— 

Benzyl  chloride 


-CH2-/  \ 

)i-phenyl  methane 

In  this  compound  the  benzyl  group  is  linked  to  the  phenyl  group  or 
the  two  benzene  rings  are  linked  by  an  intervening  methylene  group. 
Considering  the  methylene  group  as  a  residue  of  methane  the  com- 
pound is  plainly  di-phenyl  methane.  This  is  the  name  by  which  it  is 
known. 

By  Friedel-Craft  Reaction.  —  The  best  method  of  preparing  the 
compound  is  by  the  Friedel-Craft  reaction  from  benzene  and  benzyl 
chloride  or  by  the  same  reaction  from  benzene  and  di-chlor  methane. 


C6H5—  CH2—  (Cl  +  H)—  C6H5         C6H5—  CH2—  C6H5 

Benzyl  chloride  Benzene  Di-phenyl  methane 


C6H5—  H  +  Cl—  CH2—  Cl  +  H—  C6H5  —    C6H5—  CH2—  C6H5 

Benzene  Di-chlor  methane  Benzene 

Benzophenone.  —  This  last  synthesis  proves  conclusively  that  it  is 
a  di-phenyl  substituted  methane.     Di-phenylme  thane   is  a  crystalline 


734  ORGANIC  CHEMISTRY 

compound,  m.p.  26°,  with  an  odor  of  oranges.  When  it  is  oxidized 
the  methylene  group  is  affected  with  the  replacement  of  the  two  hydro- 
gens by  one  oxygen  yielding  benzophenone  (p.  657). 

+  O 

C6H5— CH2— C6H5   7=1    C6H5— CO— C6H5 

Di-phenyl  methane  ,     TT  Benzophenone 

Conversely  we  may  obtain  the  hydrocarbon  from  the  ketone  by 
reduction. 

Eluorene. — We  stated  that  when  benzene  is  passed  through  a  red 
hot  tube  two  molecules  lose  two  hydrogens  with  the  formation  of  di- 
phenyl.  Di-phenyl  methane  acts  in  the  same  way,  one  molecule  losing 
two  hydrogens,  one  from  each  ring  from  the  positions  ortho  to  the  methy- 
lene linkage,  the  new  hydrocarbon  being  known  as  fluorene. 

/~~\    -*«     /~A 

CH2-(              }          -*../  )- 

\ /  \ /redhottube\ / 

Di-phenyl  methane  \  / 

Fluorene 

Dyes.  Auramine. — A  hydrocarbon  which  is  very  closely  related 
to  di-phenyl  methane  and  which  we  shall  study  very  soon  is  tri-phenyl 
methane.  It  is  the  mother  substance  of  a  large  and  very  valuable 
group  of  dyes.  While  di-phenyl  methane  also  yields  dyes  they  are  few 
in  number.  They  are  known  as  auramine  dyes.  The  dye  known  as 
auramine  O  is  made  as  follows:  Michler's  ketone  (p.  667),  which  is 
tetra-methyl  di-amino  benzo  phenone,  is  heated  with  ammonium 
chloride  and  anhydrous  zinc  chloride.  The  ammonium  chloride  yields 
ammonia  which  reacts  with  the  ketone  with  the  loss  of  water,  the  zinc 
chloride  being  the  dehydrating  agent. 

(4)  (CH3)2N— C6H4— C— C6H4— N(CH3)2  (4)  +  (H2)— NH      — -> 

Ammonia 

(O) 

Tetra-methyl  di-amino 
Benzophenone, 
Michler's  ketone 

(4)  (CH3)2N-C6H4-C-C6H4-N(CH3)2  (4) 

II 
NH 

Auramine    (base) 


DI-PHENYL  AND  RELATED  COMPOUNDS 


735 


The  auramine  base  as  formed  in  this  reaction  is  not  itself  a  dye.     The 
actual  dye  is  the  hydro-chloride  salt. 


Auramine  O 

(salt) 


=  N=(CH3)2 


The  discussion  of  the  constitution  of  this  and  related  dyes  will  be 
taken  up  with  the  tri-phenyl  methane  dyes.  Di-phenyl  ethane,  the 
next  higher  homologue  analogous  to  di-phenyl  methane,  is  also  known 
in  isomeric  forms  similar  to  the  symmetrical  di-chlor  ethane  or  ethylene 
chloride  and  the  unsymmetrical  di-chlor  ethane  or  ethylidene  chloride. 

C6H5 
Tri-phenyl  Methane,  C6H5— CH/ 

C6H6 

Synthesis. — This  hydrocarbon  is  by  far  the  most  important  of 
those  in  which  two  or  more  benzene  rings  are  linked  together  by  inter- 
vening aliphatic  carbon  groups.  Just  as  methyl  chloride  and  benzene 
by  the  Friedel-Craft  reaction  yield  phenyl  methane  (methyl  benzene 
or  toluene);  and  methylene  chloride,  di-chlor  methane,  with  benzene 
yields  di-phenyl  methane ;  so  by  the  same  reaction  tri-chlor  methane, 
chloroform,  yields  with  benzene  a  hydrocarbon  which  by  this  synthesis 
must  be  tri-phenyl  methane. 

C6H5 — (H        Ck  .    .    .  ,          CeHj^ 

C6H5—  (H  +  ClAcH          ^_!r          C.H5-OCH     +     3HC1 

C6H6— (H        Cr  CelV 

Benzene  Chloroform  Tri-phenyl  methane 

(3  mol.) 

It  may  be  synthesized  also  from  benzal  chloride  and  benzene  by  the 
Friedel-Craft  reaction,  or  from  benzaldehyde  and  benzene  by  heating 
with  anhydrous  zinc  chloride  to  25O°-27O°. 


736  ORGANIC  CHEMISTRY 

H)—  C6H5     (AlClj) 
C6H5—  CH=(C12+  --  >     C6H5—  CH  +  3HC1 

(OH)—  C6H5    (ZnC12)  NC6H6 

Benzal  chloride  Benzene  Tri-phenyl  methane 

or  Benzaldehyde  (2  mo/.) 

Tri-phenyl  methane  is  a  solid  crystallizing  in  various  forms,  m.p.  92°, 
b.p.  358°.  It  is  quite  easily  soluble  in  ether  or  benzene  but  only  slightly 
in  alcohol.  When  reduced  by  means  of  phosphorus  and  hydriodic 
acid  it  yields  benzene  and  toluene. 

C*  TT 
C6H5—  CH<f          +  H  (HliP)  C6H5—  CH3  +  2C6H6 

N^.  TT  Toluene  Benzene 

CeHs 
Tri-phenyl  methane 

TRI-PHENYL  METHANE  DYES 

The  importance  of  tri-phenyl  methane  is  in  its  relation  to  a  large 
number  of  very  valuable  dyes  which  are  known  as  the  tri-phenyl 
methane  dyes  and  which  include  several  smaller  groups  known  as  the 
rosaniline,  para-rosaniline,  malachite  green,  rosolic  acid  and  phthalein 
dyes.  The  relationship  between  these  dyes  and  tri-phenyl  methane 
has  been  worked  out  in  an  exceedingly  interesting  manner.  We  shall 
not,  however,  attempt  to  present  the  matter  in  its  historical  connection 
but  will  show  the  steps  in  the  relationships  as  they  have  been  worked 
out  at  various  times,  disregarding  altogether  any  chronological  sequence 
in  their  order. 

Methane  Character.  —  Tri-phenyl  methane  is  the  hydrocarbon 
mother  substance  from  which  the  dyes  are  derived.  The  relation  be- 
tween the  hydrocarbons,  methane,  toluene,  di-phenyl  methane  and 
tri-phenyl  methane  is  clearly  seen  if  we  write  their  formulas  as  deriva- 
tives of  methane. 


H—  CH          H—  C-H  H—  C 

XH  XH  XH  XC6H5 

Methane  Toluene  Di-phenyl  Tri-phenyl 

Phenyl  methane  methane  methane 

Oxidation  Products.  —  Methane  stands  at  one  end,  as  a  pure  ali- 
phatic hydrocarbon,  while  the  others  are  phenyl  derivatives  becoming 
more  strongly  aromatic  in  character,  but  retaining,  even  in  tri-phenyl 
methane,  at  least  one  methane  hydrogen.  Thus  toluene,  di-phenyl 
methane  and  tri-phenyl  methane  exhibit,  in  the  order  given,  a  grad- 


TRI-PHENYL  METHANE  DYES 


737 


ually  decreasing  aliphatic  character.     This  is  most   clearly  shown  in 
the  oxidation  products  which  may  be  presented  as  follows: 

Oxidation  Products 

OH 

->  o=c< 

XH 

Formic  acid 


,H 


H— CM 


SH 


Methane 


/£*&* 
H— CMH 

XH 

Toluene 


HO— C^-H 
XH 

Methyl  alcohol 

(primary) 


o=c<x 

VH 

Formaldehyde 


H— G 

Di-phenyl  methane 


TT f-\/     f^     TT 

M— U    L6H5 
XC6H5 

Tri-phenyl  methane 


HO— C^-H 
XH 

Benzyl  alcohol 

(primary) 

/c& 

HO— C^C6H5 
XH 

Benzhydrol 

(secondary 
alcohol) 


yCeHs 

"\ r*s     TT 

J  —  i^     n. 

Benzaldehyde 


OH 


Benzoic  acid 


XC6H5 

Benzo  phenone 

(ketone) 


HO— C^C6H5 
XC6H5 

Tri- 


enyl 
carbinol 

(tertiary  alcohol) 


These  relationships  are  exactly  analogous  to  those  between  primary, 
secondary  and  tertiary  hydrocarbons  and  alcohols  (Part  I,  p.  123). 
The  first  two,  viz.,  methane  and  toluene,  are  primary  hydrocarbons 
each  containing  a  carbon  with  three  remaining  hydrogens  linked  to  it. 
They  yield  primary  alcohols,  aldehydes  and  acids.  Di-phenyl  methane 
is  a  secondary  hydrocarbon  containing  only  two  remaining  hydrogen 
atoms  linked  to  the  aliphatic  carbon  and  it  yields  a  secondary  alcohol 
and  a  ketone.  The  fourth,  tri-phenyl  methane,  is  a  tertiary  hydro- 
carbon containing  one  hydrogen  only,  which  is  linked  to  the  aliphatic 
carbon,  and  therefore  it  is  capable  of  oxidation  only  to  a  tertiary 
alcohol  or  carbinol.  The  relation  of  this  carbinol  to  the  hydrocarbon 
and  its  derivatives  we  shall  find  to  be  very  important. 

Benzene  Character. — The  three  hydrocarbons  which  contain  ben- 
zene rings,  viz.,  toluene,  diphenyl  methane  and  tri-phenyl  methane, 
all  act  like  benzene  and  yield  characteristic  benzene  derivatives.  Those 
of  especial  importance  are  the  nitro  and  amino  ring  substitution 
products. 

47 


738  ORGANIC  CHEMISTRY 

Para-rosaniline 

Tri-nitro  Tri-phenyl  Methane.  —  When  tri-phenyl  methane  is 
nitrated  a  tri-nitro  tri-phenyl  methane  is  obtained  in  which  one  nitro 
group  enters  each  benzene  ring. 

Tri-aminoTri-phenyl  Methane.  —  This  on  reduction  passes  to  the 
corresponding  tri-amino  tri-phenyl  methane. 


4—  N02(4) 

H—  CC6H5  +  3HO.NO2    -  >    H—  CC6H4—  NO2(4)  +  H       -» 
XC6H5  XC6H4—  N02(4) 

Tri-phenyl  Tri-nitro  tri-phenyl 

methane  methane 

XC6H4-NH2(4) 

H—  C<^C6H4—  NH2(4) 

XC6H4-NH2(4) 

Tri-amino 
tri-phenyl  methane 

Furthermore,  it  has  been  shown  that  the  three  nitro  and  the  three  amino 
groups  are  in  the  para  positions  in  the  benzene  rings.  The  full  struc- 
tural formula  for  the  tri-amino  tri-phenyl  methane  is,  therefore, 


— NHS 


n  XTTJ     Tri-amino  tri-phenyl  methane 

Jtl — \^~  \  / — JNrio     — ^  ...        f,  ,       \ 

Para-rosanmne  (leuco  base). 


Para-rosaniline,  Leuco  Base. — This  compound,  viz.,  the  p$-tri- 
amino  derivative  of  the  hydrocarbon  tri-phenyl  methane,  is  the  more 
immediate  mother  substance  of  a  dye  known  as  para-rosaniline.  It 
is  termed  the  leuco  base  of  the  dye. 

Tri-amino  Tri-phenyl  Carbinol.  Carbinol  Base. — When  tri-amino 
tri-phenyl  methane  is  oxidized  it  yields  a  carbinol  or  alcohol  just  as 
tri-phenyl  methane  itself  does,  viz., 


TRI-PHENYL  METHANE  DYES 


739 


HO— Ci 


— NIL 


-NH    Tri-amino  tri-phenyl  carbinol, 
Para-rosaniline  (carbinol  base) 


— NH2 


Para-rosaniline  Chloride. — This  carbinol  is  known  as  para-rosaniline, 
carbinol  base.  It  is  not  a  dye  but  when  treated  with  acids  it  yields 
salts  which  are  colored  and  which  possess  the  properties  of  dyes.  These 
salts  result  from  one  of  the  amino  groups  reacting  with  the  acid,  forming 
an  ammonium  salt,  the  tri-valent  nitrogen  of  the  amine  becoming 
penta-valent  in  the  salt,  as  in  the  formation  of  methyl  ammonium 
chloride  from  methyl  amine. 


CH3— N<f       +  HC1 
H 

Methyl  amine 

XC6H4-NH2(4) 
HO— C/-C6H4— NH2(4) 

XC6H4— NH2(4)  +  H— Cl 

Tri-amino  tri-phenyl  carbinol 
Para-rosaniline  (carbinol  base) 


CH3— N= 


H 
H 

Cl 


Methyl  ammonium  chloride 


,C6H4-NH2(4) 


(HO)—  C^- 


•C6H4—  N 

I 
Cl 

Hydrate  salt 


2(4) 

H 
H 

(H) 


-H20 


\\_-/ 


-NH2 


— NH2 


w 


H 


Cl 

Anhydride  sail 
Para-rosaniline  chloride 


740  ORGANIC  CHEMISTRY 

In  the  above  reaction  there  is  first  formed,  in  the  cold,  a  hydrate  salt 
which  is  colorless.  This  on  heating  loses  water,  as  indicated,  yielding 
an  anhydride  salt  which  is  the  dye  and  has  the  constitution  as  given. 
The  formation  of  this  anhydride  dye  salt  involves  the  conversion  of  one 
of  the  benzene  rings  from  the  normal  structure  with  alternate  double 
and  single  bonds  to  a  structure  found  in  quinone  (p.  636). 

O 


C 


O 

Quinoid  Structure  of  Dyes. — This  is  known  as  the  quinone  or 
quinoid  structure  and,  according  to  theories  regarding  the  relation 
between  constitution  and  color  in  compounds  possessing  properties  of 
dyestuffs,  it  is  the  presence  of  a  group  with  this  structure  which  endows 
the  dyes  of  this  and  related  classes  with  color. 

Chromophore. — Such  a  group  is  termed  a  chromophore  and  each 
large  group  of  dyes  has  a  characteristic  chromophore. 

Considering  again  what  we  have  brought  out  in  connection  with 
para-rosaniline  we  should  note  that  there  are  four  distinct  compounds, 
viz.,  the  amine  base  or  leuco  base,  the  carbinol  base,  the  hydrate  salt 
and  the  anhydride  salt  or  dye.  Now  these  four  types  of  compounds  are 
known  not  only  in  the  case  of  para-rosaniline  but  in  the  case  of  all  tri- 
phenyl  methane  dyes.  The  general  characters  of  these  four  types  of  tri- 
phenyl  methane  derivatives,  including  their  color  properties  which  are 
very  important,  may  be  given  as  follows: 

Leuco  Base. — (i)  The  amine  base  is  the  simple  amine  substitution 
product  of  the  hydrocarbon  tri-phenyl  methane.  It  may  be  obtained 
by  reducing  the  other  compounds  and  is  thus  the  reduction  product. 
It  is  colorless  and  is  termed  the  leuco  base,  the  word  leuco  meaning 
colorless. 

Carbinol  Base. — (2)  The  carbinol  base  is  the  alcohol  or  hydroxyl 


TRI-PHENYL  METHANE  DYES 


741 


compound  resulting  from  the  oxidation  of  the  amine  base.  It  is  usually 
colorless  and  is  termed  the  color  base  or  carbinol  base. 

Colorless  Hydrate  Salt. — (3)  The  hydrate  salt  is  formed  from  the 
carbinol  base  by  addition  of  acid.  It  is  colorless  or  with  slight  color. 
It  may  be  present  in  the  cold  solution  but  on  heating  readily  loses  water 
yielding  the  last  form. 

Colored  Dye  Salt. — (4)  The  anhydride  salt  formed  by  loss  of  water 
from  the  hydrate  salt.  It  has  the  quinoid  structure  in  the  benzene  ring 
linked  to  the  ammonium  salt  group.  This  compound  is  colored  and  is 
the  dye  salt  or  the  actual  dye.  The  formulas  of  the  para-rosaniline 
compounds  may  be  given  all  together  as  follows: 


-NH2 


H— 


-NH2     HO— C; 


A  mine 


— NH2 


Carbinol 


-NH< 


Tri-amino  tri-phenyl  methane 

Leuco  base  of  para-rosaniline 
Colorless 


Tri-amino  tri-phenyl  carbinol 

Color  base  of  para-rosaniline 
Colorless 


—Nil  2 


HO— C 


-NH2 


Salt 


Hydrate  salt  of  para-rosaniline 

Colorless  or  slight  color 


Anhydride  salt  of  para-rosaniline 
Colored 


742  ORGANIC  CHEMISTRY 

Preparation  of  Para-rosaniline.  —  The  synthesis  of  pararosaniline  as 
we  have  given  it,  viz.,  in  outline,  from  tri-phenyl  methane  --  >tri- 
nitro  tri-phenyl  methane,  -  >tri-amino  tri-phenyl  methane,  -  >tri- 
amino  tri-phenyl  carbinol  -  ^colorless  hydrate  salt  -  ^anhydride  salt 
or  dye,  was  developed  during  the  study  of  the  constitution  of  the  com- 
pound and  establishes  its  constitution  as  we  have  given  it.  This  syn- 
thesis is  not,  however,  a  practical  one  for  the  commercial  preparation 
of  the  dye.  The  method  now  used  is  in  effect  the  same  as  was  used  in 
the  discovery  of  the  substance  though  its  explanation  is  the  result  of 
the  constitutional  study  which  led  to  the  synthesis  above.  When  two 
molecules  of  aniline  and  one  molecule  of  p-toluidine  are  treated  with  an 
oxidizing  agent,  e.g.,  arsenic  oxide  chromic  acid,  or  mono-nitro  benzene, 
the  leuco  base  of  para-rosaniline  is  obtained.  In  the  light  of  the  con- 
stitution of  the  leuco  base  as  we  have  given  it  the  reaction  may  be 
represented  as  follows: 

(H    H)C6H4—  NH2  Aniline 

(O)           |  /CeH,—  NH2(4) 

||    +  HC—  C6H4—  NH2(4)   p-Toluidine  -»    HC^C6H4—NH2(4) 

(O)           |  XC6H4—  NH2(4) 

(H      H)CeH4—  NH2    Aniline  P-P-p-Tr^mm^tri-phenyl 

Oxy-  Leuco-base,  Para-rosaniline 

gen 

It  is  probable  that  the  reaction  proceeds  in  two  steps:  first,  the 
p-toluidine  has  the  methyl  group  oxidized  to  the  aldehyde  group  yield- 
ing p-amino  benzaldehyde;  second,  this  aldehyde  then  reacts  with  aniline 
just  as  benzaldehyde  does  with  benzene  in  the  synthesis  of  tri-phenyl 
methane  (p.  735). 

H)—  C6H4—  NH2 

H3C—  C6H4—  NH2(4)  +  O  -  >  (0)  =  HC—C6H4—  NH2(4)  -  H2O 

H)—  C6H4—  NH2 

p-Toluidine  p-Amino  benzaldehyde 

+Aniline  (2  wo/.) 

—  NH2(4) 

—  NH2(4) 
NH2(4) 


64— 
XC6H4— 


Leuco-base,  Para- 
rosaniline 


It  is  clear  that  the  aliphatic  carbon  atom  of  the  leuco  base  is  the  ali- 


TRI-PHENYL  METHANE  DYES 


743 


phatic  methyl  carbon  atom  of  p-toluidine.  That  this  methyl  carbon  in 
toluidine  is  para  to  the  amino  group  is  in  agreement  with  the  consti- 
tution of  the  leuco  base  and  with  the  fact  that  p-toluidine  will  thus 
yield  the  leuco  base  while  0-toluidine  will  not.  The  conversion  of  the 
leuco  base  into  the  dye  salt  is  accomplished  by  further  oxidation  to  the 
carbinol  base  and  treatment  of  this  with  acid  and  heat  yielding  the 
anhydride  salt  or  dye.  These  reactions  need  not  be  repeated. 

An  interesting  historical  fact  is  that  the  original  preparation  of  the 
dye  was  by  the  oxidation  of  crude  aniline  alone.  Then  it  was  shown 
that  pure  aniline  did  not  yield  the  dye  and  that  the  crude  compound, 
which  did  yield  the  dye,  always  contained  p- toluidine  also.  Thus  the 
latter  compound  is  absolutely  essential  to  the  synthesis.  The  original 
crude  preparation,  the  synthetic  commercial  preparation  and  the 
synthesis  from  tri-phenyl  methane  all  agree  and  are  in  accord  with  the 
established  constitution.  The  name  para-rosaniline  was  given  to  the 
dye  because  para~to\mdine  is  an  essential  synthetic  constituent. 

Rosaniline 

When  the  dye  that  was  made  by  oxidizing  crude  aniline  was  studied 
and  the  facts  which  we  have  stated  were  determined,  it  was  also  found 
that  the  dye  was  not  one  compound  but  that  two  were  present  as  a 
mixture.  Originally  the  mixture  of  the  two  was  called  simply  rosani- 
line,  but  to  distinguish  the  two  compounds  the  one  we  have  been  study- 
ing because  of  its  relation  to  para-toluidine  is  called  para-rosaniline 
while  the  other  is  named  simply  rosaniline.  Sometimes  the  name 
rosaniline  is  applied  to  the  former  and  the  latter  is  then  called  homoros- 
aniline.  The  first  names  are  the  better  and  are  now  generally  adopted. . 

Rosaniline  then  is  another  dye  compound  related  to  para-rosaniline. 
It  is  not  isomeric  but  differs  in  composition  by  CH2.  This  at  once 
suggests  that  it  is  a  homologue  and  such  has  been  found  to  be  the  case. 
Its  constitution  has  been  established  by  its  synthesis  from  pure  com- 
pounds. When,  instead  of  using  two  molecules  of  aniline  and  one 
molecule  of  />-toluidine  as  in  the  synthetic  preparation  of  para-rosaniline, 
we  use  one  molecule  each  of  aniline,  p-toluidine  and  ortho -toluidine 
then  we  obtain  the  leuco  base  of  rosaniline  alone.  From  the  leuco 
base  the  dye  salt  is  obtained  by  the  usual  methods.  The  reactions 
analogous  to  the  ones  for  para-rosaniline  are: 


744  ORGANIC  CHEMISTRY 


3)  /  CH3(3) 

/TT       TT^ C*  TT  r  P^TToC 

V^rl        -Cly ^G-^-SV  /^6J-L3\. 

(O)      I                         XNH2(4)  NNH2(4) 

||   +  CH-C6H4-NH2(4) >H-CY-C6H4-NH2(4) 

(O)      |  \                                 +heat 

(H    H)— C6H4— NH2  XC6H4— NH2(4) 

Aniline  (i  mol.)  Rosaniline 

£-Toluidine  (i  mol.)  Leuco  base 
Oxygen                    o-Toluidine  (i  mol.) 


The  constitution  of  rosaniline  as  the  ortho-mono-methyl  homologue 
of  para-rosaniline  has  been  fully  established.  We  thus  see  that  for  the 
preparation  of  rosaniline  both  ortho-  and  />ara-toluidine  are  essential  and 
this  has  been  found  to  be  the  fact  as  neither  one  alone  will  yield  this 
dye.  The  obtaining  of  both  dye  compounds  in  the  preparation  from 
crude  aniline  is  explained  by  the  fact  that  this  substance  is  a  mixture  of 
not  only  aniline  and  />ara-toluidine  but  or/^-toluidine  also.  Crude 
aniline  is  commercially  termed  aniline  for  red  (p.  544),  the  significance 
of  which  is  plain  as  these  dyes  obtained  from  it  are  of  a  general  red 
color. 

Historical. — While  it  is  not  desirable  to  discuss  at  length  the 
historical  development  of  the  dyes  known  in  general  as  aniline  dyes  it 
will  be  of  interest  to  mention  some  of  the  leading  facts,  especially  those 
connected  with  the  class  of  dyes  which  we  are  now  considering. 

Perkin,  Mauve. — In  1856  Perkin  (Sir.  Wm.  Perkin),  while  investi- 
gating quinine  and  attempting  to  prepare  it  by  the  oxidation  of  allyl 


TRI-PHENYL  METHANE  DYES  745 

toluidine,  found  that  when  crude  aniline  was  oxidized  with  chromic 
acid  a  colored  product  was  obtained  which  he  succeeded  in  isolating  as 
a  rose-violet  dye  and  to  which  he  gave  the  name  mauve.  The  pro- 
cess was  patented  in  England  and  the  dye  was  made  and  used  for  a 
considerable  time.  At  present  it  is  not  made  or  used  to  any  extent. 
This  dye  mauve  was  the  first  aniline  dye  or  chemically  prepared  dye  to 
be  made  and  its  discovery  and  commercial  preparation  mark  an 
epoch  in  industrial  chemistry  and  the  beginning  of  what  is  usually 
termed  the  aniline  dye  industry.  The  branch  of  industrial  chemistry 
thus  opened  is  perhaps  without  a  parallel  in  the  variety,  usefulness  and 
value  of  the  products  obtained.  The  recognition  of  the  importance 
of  the  discovery  was  made  in  1906,  on  its  50  year  anniversary,  by  a 
Jubilee  Celebration  in  England,  America  and  Germany  at  which  the 
discoverer  was  honored  and  congratulated  by  various  societies  espe- 
cially the  Society  of  Chemical  Industry  of  England  and  America,  The 
American  Chemical  Society  and  Die  Deutsche  Chemische  Gesell- 
schaft. 

Perkin  Medal. — The  American  Society  of  Chemical  Industry 
established  a  medal  known  as  The  Perkin  Medal  the  first  impression 
of  which  was  presented  to  Sir  Wm.  Perkin  in  person.  The  medal  is 
now  awarded  annually  to  the  American  chemist  who  has  contributed 
the  most  important  work  on  industrial  chemistry.  The  men  who  have 
been  awarded  the  medal,  up  to  1921,  are  the  following: 

1906  Sir  William  Perkin ;  The  Discovery  of  Mauve,  the  First  Aniline  Dye. 

1908  J.  B.  F.  Herreshoff ;  Contact  Process  for  Sulphuric  Acid. 

1909  Arno  Behr;  Com  Products  Industry. 

1910  E.  G.  Acheson;  Carborundum  and  Artificial  Graphite. 

1911  Charles  M.  Hall ;  Aluminium. 

1912  Herman  Frasch;  Desulphurized  Petroleum  and  Louisiana  Sulphur. 

1913  James  Gayley;  Dry  Blast  Iron  Smelting. 

1914  John  W.  Hyatt;  Celluloid  and  Flexible  Roller  Bearings. 

1915  Edward  Weston;  Contributions  to  Electro  Chemical  Industry. 

1916  L.  H.  Baekeland;  Photography,  Electro  Chemistry  and  Plastics  (Velox  and 

Bakelite). 

1917  Ernest  Twitchell;  Fats,  Soap  and  Glycerol. 

1918  Auguste  J.  Rossi;  Titanium  and  Titaniferous  Iron  Ores. 

1919  Frederick  G.  Cottrell;  Electrical  Precipitation  of  Suspended  Particles. 

1920  Charles  F.  Chandler;  General  Industrial  Chemistry. 

1921  Willis  R.  Whitney;  Industrial  Research. 

The  dye  mauve  is  not  a  tri-phenyl  methane  compound  and  so  does 


746  ORGANIC  CHEMISTRY 

not  belong  to  the  same  group  of  dyes  as  do  the  rosanilines  but  its  dis- 
covery led  to  investigations  from  which  the  latter  dyes  resulted. 

Fuchsin,  Magenta. — In  1859  Verguin  in  France  found  that  crude 
aniline  oxidized  by  means  of  stannic  chloride  yielded  a  red  dye  which 
was  named  fuchsin  and  also  magenta.  Other  oxidizing  agents  were 
used  later,  e.g.,  mercuric  chloride,  arsenic  acid,  mono-nitro  benzene. 

Hofmann. — In  1862  Hofmann,  whose  name  is  always  associated 
with  the  development  of  our  ideas  in  regard  to  the  constitution  of 
amines;  showed  that  the  red  dye  obtained  was  a  salt  of  a  base  which  he 
named  rosaniline  and  later  that  />-toluidine,  always  a  constituent  of 
crude  aniline,  was  essential  to  the  formation  of  the  dye. 

Fischer. — Later  Emil  and  Otto  Fischer,  the  former  being  the  one 
to  whom  we  have  repeatedly  referred  in  connection  with  uric  acid, 
carbohydrates  and  proteins,  proved  that  the  constitution  of  para- 
rosaniline  was  as  we  have  previously  given  it  and  developed  the  methods 
of  synthesis. 

Caro,  Rosenstiehl,  Schorlemmer,  Hantzsch,  Nietski. — A  few  other 
chemists  whose  names  belong  in  any  list  of  those  who  have  developed 
the  aniline  dye  industry  may  also  be  mentioned.  The  first  three  were 
concerned  principally  with  the  dyestuff  industry,  while  the  last  two 
developed  theories  in  regard  to  the  relationship  between  constitution 
and  color  in  dye  compounds. 

The  rosaniline  dye  first  obtained  was  probably  a  mixture  of  salts 
of  both  para-rosaniline  and  rosaniline.  The  names  given  to  it  at  the 
beginning,  viz.,  fuchsin  and  magenta,  are  still  used.  Acid  fuchsin,  a 
common  form  of  the  dye,  is  a  mixture  of  the  sodium  salts  of  the  mono- 
and  di-sulphonic  acid  derivatives  of  para-rosaniline  and  rosaniline. 

Formaldehyde  and  Phosgene  Methods. — Two  other  processes  for 
the  commercial  preparation  of  fuchsin  are  the  formaldehyde  and  the 
phosgene,  COC12,  processes.  For  details  in  regard  to  them  special 
books  on  dyes  should  be  consulted,  e.g.,  Cain  &  Thorpe. 

Synthetic  Dyes. — In  common  usage  the  term  aniline  dye  is  applied 
to  any  dyestuff  prepared  from  organic  chemical  substances.  As  the 
first  dye  made  and  many  of  those  made  at  present  are  derived  from  ani- 
line the  above  name  is  significant.  It  is  not  a  true  name,  however,  in 
many  cases  for  though  some  of  the  azo  and  benzidine  dyes  (p.  573) 
may  be  considered  as  aniline  derivatives  those  derived  from  naphtha- 
lene can  not  be  so  considered.  Other  dyes  which  we  shall  study  later, 


TRI-PHENYL  METHANE  DYES  747 

e.g.,  alizarin,  are  in  no  sense  aniline  products.  All  of  the  compounds 
from  which  the  chemical  dyes  are  made  are,  however,  obtained  either 
directly  or  indirectly  from  coal  tar  (p.  494),  and  the  name  coal  tar  dyes 
is  better  than  aniline  dyes  in  designating  the  entire  class.  The  name 
chemical  dyes  is  also  sometimes  used  but  the  best  name  on  the  whole  is 
Synthetic  Dyes  as  including  any  dyestuff  made  by  chemical  processes 
and  not  from  a  natural  plant  source,  e.g.,  natural  indigo,  turkey  red, 
etc.,  or  animal  source,  e.g.,  cochineal  or  natural  Tyrean  purple.  Such 
a  name  might  be  taken  to  include  inorganic  coloring  substances  but  the 
term  dye  is  restricted  to  organic  compounds  with  color  which  color  is 
able  to  be  fixed  upon  animal  or  vegetable  fibers.  The  synthetic  dyes 
include  colors  of  practically  every  conceivable  tint  or  shade  and  in 
their  technical  treatment  for  dyeing  fibers  are  of  various  groups.  Fur- 
ther discussion  of  the  general  subject  of  dyes  is  not  desirable  in  this 
text  but  may  be  found  in  special  works  on  the  subject  as  mentioned  in 
the  list  of  references  (p.  910). 

• 
Malachite  Green 

Another  group  of  dyes  belonging  to  the  tri-phenyl  methane  series 
but  which  differ  from  the  rosanilines  in  not  being  derived  from  tri- 
amino  tri-phenyl  methane  is  represented  by  malachite  green.  It  is 
one  of  the  oldest  of  the  synthetic  dyes,  having  been  first  prepared  by 
O.  Fischer  in  1877.  The  immediate  mother  substance  is  di-amino 
tri-phenyl  methane  of  which  the  leuco  base  of  the  dye  is  the  tetra- 
methyl  derivative. 


/C6H5  / 

HcA:6H4-NH2(4)       ->    Hcf  C6H4-N(CH3)2(4) 
\C6H4-NH2(4)  \C6H4-N(CH3)2(4) 

Di-amino  tri-phenyl  Leuco  base  ot  Malachite 

methane  Green 

It  is  prepared  as  follows:  Di-methyl  aniline,  two  molecules,  and 
benzaldehyde,  one  molecule,  are  heated  with  zinc  chloride  or  hydro- 
chloric acid.  Condensation  with  the  loss  of  water  takes  place  and 
the  leuco  base  of  malachite  green  is  obtained.  The  oxidation  of  the 
leuco  base  to  the  carbinol  base  is  accomplished  with  lead  peroxide, 
PbO2. 


748 


ORGANIC  CHEMISTRY 


H) 


-N(CH3)2 


..      H/  VN(CH3); 

Benzaldehyde  +  Di-methyl  aniline 

(i  mol.)  (2  mol.) 


,rv  JBaW-pW  —  4(  )-N(CH3)2(4) 

\\ /          HC1  \\ / 

>r^. 


N(CH,),(4) 


v^ 

Leuco  base 


=  N=(CH3)2(4) 


Malachite  Green  Dye  salt  Cl 


Trie  dye  salt  may  be  obtained  as  the  chloride  or  acetate  but  usually  in 
beautiful  green  crystals  of  the  oxalate  or  as  the  double  chloride  with 
zinc.  Other  derivatives  corresponding  to  malachite  green  are  dyes  of 
various  shades  of  green  and  blue. 

Rosolic  Acid 

A  third  group  of  dyes  belonging  to  the  tri-phenyl  methane  series 
yet  differing  from  both  rosaniline  and  malachite  green  is  the  rosolic  acid 
group  which  are  known  as  aurines.  Two  dyes  are  known  analogous  to 
para-rosaniline  and  rosaniline.  They  are  para-rosolic  acid  and  rosolic 
acid,  the  latter  being  the  methyl  substitution  product  of  the  former. 


TRI-PHENYL  METHANE  DYES 


749 


The  leuco  base  of  para-rosolic  acid  is  the  tri-hydroxytri-phenyl  methane 
as  is  proven  by  its  formation  from  para-rosaniline  leuco  base  by  diazotiz- 
ing  and  then  decomposing  the  diazo  compound  with  water  (p.  597). 


XC6H4-NH2(4)  diazo_ 
/  ^  "      NH2(4)  -    -> 
NH2(4)     tize 

H2O 


\ 


CeH4 — I-N  xi2 

Para-rosaniline 

Leuco  base 


•H(4) 


+O 

OH(4)         _, 
-H2O 


0(4) 


Rosolic  acid 

Aurine 

Dye 


The  dye  compound  which,  strictly  speaking,  is  not  a  salt  but  a  quinone  is 
obtained  directly  by  oxidizing  the  leuco  base,  the  intermediate  carbinol 
losing  water  without  the  action  of  an  acid.  Dyes  of  this  group  are  not 
very  numerous,  rosolic  acid  itself  being  used  chiefly  as  an  indicator.  It 
is  interesting  that  the  compound  was  prepared  long  before  Perkin, 
Hofmann  and  Fisher  made  the  first  actual  synthetic  dye  and  established 


750 


ORGANIC  CHEMISTRY 


the  constitution  of  the  rosanilines.     It  was  first  prepared  by  Runge  in 
1834  being  one  of  the  very  oldest  dye  compounds. 


PHTHALEIN  DYES 
Phenolphthalein 

An  important  group  of  dyes  known  as  the  phthaleins  and  typified 
by  the  common  indicator  phenolphthalein  are  derivatives  of  tri-phenyl 
methane,  but  because  they  do  not  possess  the  same  structure  as  the 
three  preceding  groups  are  placed  in  a  separate  series  known  as  the 
pyronines. 

Preparation  from  Phthalic  Acid.  —  In  discussing  phthalic  acid 
(p.  691)  we  spoke  of  the  fact  that  phthalic  anhydride  or  phthalyl 
chloride  with  phenol  yields  phenolphthalein.  The  reaction  takes  place 
in  the  presence  of  anhydrous  zinc  chloride  as  a  dehydrating  agent  or  in 
the  presence  of  aluminium  chloride  (Friedel-Craf  t)  .  Phthalyl  chloride 
being  the  unsymmetrical  compound  (p.  692),  the  two  reactions  are 
represented  as  follows: 


(O) 


C6H 


H)—  C6H4OH 
H)-C6H4OH 


C6H4—  OH      (4) 


^i2)      C6H/ 


C-C6H4-OH(4) 


heat 


O 

Phthalic  anhydride 


(Cl 
I 


Phenol 

H)—  C6H4—  OH 


H/    >0 
X 


O 

Phthalyl  chloride 


Cl      H)-C6H4-OH 


O 

Phenolphathalein 

C6H4—  OH      (4) 

I 
Cr-C6H4-OH(4) 


C6H 


O 


Tri-phenyl  Methane  Derivative.  —  That  this  compound  is  a  deriva- 
tive of  tri-phenyl  methane  is  proven  by  the  following  series  of  relation- 
ships. When  phthalyl  chloride  is  reduced  with  hydrogen  we  obtain 
phthalide  (p.  693). 


PHTHALEIN  DYES 


751 


Phthalophenone.  —  When  the  chloride  is  treated  with  ben:ene  in 
the  presence  of  aluminium  chloride  we  obtain  phthalophenone  which 
is  di-phenyl  phthalide,  these  relationships  being 

(Cl  C6H6 

H2  I  | 

(C1  H)  C6H5 
C6H 


H  6 

j  C6H/    >0     H)  C6H5  *E!  C6H 
\/ 


00  O 

Phthalide  Phthalyl  chloride  Phthalophenone 

Di-phenyl  phthalide 

Now  when  phthalophenone  is  hydrolyzed  with  alkalies  it  yields  mono- 
carboxy  tri-phenyl  carbinol  which  on  reduction  yields  mono-carboxy 
tri-phenyl  methane  and  this  by  loss  of  carbon  dioxide  yields  tri-phenyl 
methane.  This  means  that  phthalophenone  is  a  lactone  inner  anhy- 
dride of  mono-carboxy  tri-phenyl  carbinol  and  a  true  tri-phenyl  methane 
derivative  as  shown  in  the  reactions  below.  Now,  also,  phthalophenone 
by  nitrating  yields  a  di-nitro  compound  which  by  reduction  yields  a 
di-amino  derivative  and  this  by  the  diazo  reaction  has  the  two  amino 
groups  replaced  by  hydroxyls.  The  result  is  phenol  phthalein,  which 
is  therefore  also  a  lactone  inner  anhydride  of  mono-carboxy  di-hydroxy 
tri-phenyl  carbinol.  All  of  these  relationships  may  be  represented  by 
the  following: 


752 


ORGANIC  CHEMISTRY 


C6H4— COO(2) 


Phalophenone, 


Di-phenyl  phthalide 


>C«H 


HO — C\~~  C  eH  5 

XC6H4— COONa(2) 

Mono-carboxy  tri-phenyl  carbinol  (salt) 


+H 
+HC1 


xes 
H — C\~CeH5 

XCeH4— (COO)H 

Mono-carboxyjjtri-phenyl  methane 


-CO, 


xea 

H — C\~CeH5 
XC6H5 

Tri-phenyl  methane 


C6H4-N02(4) 
C6H4— N02(4) 
C6H4— COO(2) 


Di-nitro  di-phenyl  phthalide 


4— NH2(4) 
64— NH2(4) 
XC6H4— COO(2) 

I 


Di-amino  di-phenyl  phthalide 

Diazoti  zation 

and 

Decomp  osition 
with   H2O 


—  OH(4) 

—  OH(4) 
COO(2) 


64— 
XC6H4— 


Di-hydroxy  di-phenyl 

phthalide 
(Phenolphthalein 


PHTHALEIN  DYES 


753 


The  two  formulas  which  we  have  given  for  phenolphthalein  if  compared 
will  be  found  to  be  identical. 

C6H4— OH     (4) 

/C\-C6H4— OH(4)  XC6H4— OH(4) 

C6H4\    /O  Cf  C6H4-OH(4) 

CO 


(2)  , 

Phthalic  anhydride  derivative  Tri-phenyl  methane  derivative 

Phenolphthalein 

In  the  first  formula  the  starting  point  is  the  benzene  ring  of  phthalic 
anhydride  while  in  the  latter  it  is  one  of  the  carbonyl  carbons,  the 
one  which  in  phthalyl  chloride  is  linked  to  two  chlorines. 

That  a  compound  formed  from  phthalic  anhydride  and  phenol 
should  be  a  derivative  of  tri-phenyl  methane  may  at  first  seem  strange. 
If,  however,  we  recall  that  the  preparation  of  tri-phenyl  methane  and 
the  rosanilines  is  from  toluene,  or  its  derivatives,  in  which  the  methyl 
carbon  in  toluene  becomes  the  aliphatic  carbon  in  tri-phenyl  methane, 
then  we  will  recognize  that  one  of  the  carbonyl  carbons  in  phthalic 
anhydride,  which  has  its  origin  in  a  methyl  group  in  xylene,  may  also 
become  a  methane  carbon  in  a  tri-phenyl  methane  derivative.  In 
fact  from  our  reaction  between  phthalic  anhydride  and  phenol  this 
carbonyl  carbon,  which  already  has  attached  to  it  one  benzene  ring, 
has  substituted  in  place  of  the  carbonyl  oxygen  two  more  benzene  rings 
thus  linking  to  the  original  methyl  carbon  three  benzene  rings,  making 
a  tri-phenyl  methane  compound. 

Color  and  Constitution  of  Phenolphthalein. — We  have  used  phenol- 
phthalein as  an  example  of  the  phthalein  dyes  in  order  to  show  their 
relation  as  tri-phenyl  methane  derivatives.  When,  however,  we 
attempt  to  establish  a  consitution  for  phenolphthalein  which  will  ex- 
plain its  character  as  a  dye,  in  harmony  with  the  structure  of  related 
compounds,  e.g.,  fluorescein  and  other  pyronine  dyes,  we  meet  with  con- 
siderable trouble  and  it  may  be  said  that  the  question  is  one  that  does 
not  seem  to  be  cleared  up.  Strictly  speaking  phenolphthalein  is  not  a 
dye.  Its  well  known  use  as  an  indicator  is  associated  with  the  follow- 
ing facts,  (i)  In  neutral  or  acid  solution  it  is  colorless.  (2)  In  weak 
alkaline  solution  it  is  red.  (3)  In  strong  alkaline  solution  it  is  again 
colorless.  (4)  On  neutralizing  the  excess  alkali  of  (3)  with  acetic  acid 
and  boiling,  the  red  color  is  restored  and  phenolphthalein  is  precipitated. 

48 


754  ORGANIC  CHEMISTRY 

Quinoid    Structure. — The    constitutional    relationships    of   these 
changes  is  probably  as  follows: 


— 0(H) 


— ONa 


-H— OH 


-OOC 

Phenolphthalein 

(lactone  formula) 

Colorless 
Neutral  or  acid 


NaOOC 

Hydrous  salt 
Carbinol 


/              \                   +NaO 
(  )— ONa > 


NaOOC 

Anhydride  salt 

Quinoid 

Colored  red 

Weakly  alkaline 


NaOOC 

Hydrous  tri- 

sodium  salt 

Carbinol 

Colorless 

Excess  alkali 


When  neutral  or  acid  phenolphthalein,  a  lactone  inner  anhydride? 
which  is  colorless,  is  treated  with  sodium  hydroxide  to  just  alkaline 
reaction,  hydrolysis  first  takes  place  yielding  the  carbinol.  This  is 
then  neutralized  by  the  alkali  yielding  a  di-sodium  salt,  one  sodium 
entering  the  carboxyl  group  and  the  other  entering  one  of  the  phenol 


PHTHALEIN  DYES 


755 


hydroxyls.  This  salt  then  loses  water  from  the  carbinol  and  the  re- 
maining phenol  hydroxyl.  This  anhydride  has  the  quinoid  structure 
and  is  colored.  If  an  excess  alkali  is  added,  then  hydrolysis  and  neu- 
tralization again  take  place  yiedling  a  tri-sodium  carbinol  salt,  which  is 
colorless.  If  this  colorless  salt  is  neutralized  with  acetic  acid  the  color- 
less carbinol  is  first  formed  which  on  heating  loses  wateryielding  the 
lac  tone  which  is  the  original  phenolphthalein  and  which  is  precipitated. 
In  this  hydrolysis,  however,  sodium  hydroxide  is  set  free  which  reacts 
on  the  reformed  phenolphthalein  giving  the  colored  salt  again.  These 
last  changes  are: 


— ONa 


HO— C 


f      ~\-ONa(±^ 


(HO)— C 


—OH 


(-H— OH) 

—OH > 

heat 


NaOOC 

Colorless  salt 
Excess  alkali 


(H)OOC 

Colorless  carbinol 


—OH 


I 


O 


(+NaOH)         I    /  \ 

H  C'     (  Y-ONa 

(-H-OH)  V  / 


OOC 
Phenolphthalein 

(lactone) 


NaOOC 

Colored 
salt 


756  ORGANIC  CHEMISTRY 

Thus  according  to  this  view  the  change  in  color  of  phenolphthalein  is 
due  to  a  change  in  structure  from  that  of  a  lactone  to  that  of  a  compound 
containing  a  quinoid  ring.  While  this  quinoid  structure  is  like  that 
which  has  been  established  for  the  colored  dye  salts  of  the  tri-phenyl 
methane  dyes  it  has  not  been  directly  proven  in  the  case  of  phenol- 
phthalein. A  related  phthalein  made  from  hydroquinol  has  been  ex- 
plained by  a  quinoid  structure  in  which  tetra-valent  or  oxonium  oxygens 
are  present  and  also  by  a  modified  quinoid  ring  together  with  the  exist- 
ence of  a  tautomeric  compound.  Thus,  as  previously  stated,  the  exact 
constitution  of  phenolphthalein  as  a  color  compound  is  not  fully 
established. 

Dissociation  Theory. — According  to  Ostwald  the  color  changes  in 
phenolphthalein  are  explained  as  due  to  electrolytic  dissociation,  the 
negative  ion  of  the  salt  being  colored.  In  the  phenolphthalein  itself 
no  dissociation  occurs  and  the  compound  is  thus  colorless  in  neutral  or 
acid  solutions.  When  a  salt  is  formed  dissociation  takes  place  and  the 
colored  ions  produce  a  colored  solution.  This  does  not  seem  quite 
satisfactory  in  the  case  of  the  tri-sodium  salt  (p.  754)  which  evidently 
does  not  dissociate  as  the  solution  is  colorless.  This  point  is  explained 
by  the  effect  of  the  excess  of  alkali  in  retarding  dissociation. 

Pyronine  Structure. — A  study  of  related  phthaleins  has  brought  out 
a  structure  which  apparently  applies  to  all  the  dyes  of  this  group 
though  here  also  in  the  case  of  phenolphthalein  the  condition  does  not 
wholly  fit.  We  have  said  that  the  phthalein  dyes  belong  to  the  group 
known  as  pyronines.  The  pyronine  ring,  which  is  present  in  these 
compounds,  has  the  structure 


Pyronine  ring 


Rhodamines 

When  a  phthalein  is  prepared  from  phthalic  anhydride  and  ni- 
di-ethyl amino  phenol  the  product  known  as  rhodamine  has  the  struc- 
ture of  a  tri-phenyl  methane  derivative  as  follows : 


PHTHALEIN  DYES 


(A) 


N(C2H5): 


OH 
Oil 


Cf- 


— N(C2H5)2  +  HC1 


OOC 

m-Di -ethyl  ami  no  phenol  phthalein 
Rhodamine  (Leuco  base) 


-N(C2H{ 


(C) 


N(C2H6) 


o 


/ 

C/-/  \— N(C2H5)2 


Cl  or 


Cl 


,COOH 


Rhodamine 
(Dye  Salt) 


758 


ORGANIC  CHEMISTRY 


The  leuco  base  of  the  rhodamine,  (A),  is  converted  into  the  salt  by 
means  of  acids,  water  is  lost  from  the  two  neighboring  phenol  groups 
yielding  an  anhydride  linkage  of  two  of  the  benzene  rings  and  the  lac- 
tone  form  of  the  base  is  converted  into  a  quinoid  structure  in  the  salt 
(B).  If  we  write  the  formula  for  this  salt  in  a  new  way  but  expressing 
exactly  the  same  structure  as  by  the  tri-phenyl  methane  formula  (B), 
we  have  formula  (C),  which  contains  the  pyronine  ring  as  given  above. 
Now  referring  back  to  the  preparation  of  phenolphthalein  from 
phthalophenone  (p.  752),  through  the  nitro  and  amino  compounds,  we 
see  that  the  relationship  is  expressed  through  the  para-iuiro  product 
only.  However,  in  nitrating  phthalophenone  we  are  nitrating  a  ben- 
zene compound  in  which  the  rings  are  already  linked  to  a  residual 
methyl  carbon.  When  a  methyl  group  is  in  the  ring  nitration  effects 
both  the  positions  ortho  and  para  to  this  methyl  group.  It  is  found 
in  fact  that  the  ortho-mtro  derivative  is  also  present,  and  if  we  use  this 
oitho  derivative  we  obtain  finally  an  ortho  phenolphthalein  the  struc- 
ture of  which  will  be  as  in  (A)  below. 

(A)  (B) 


O 


-H— OH 


-OOC 

Hydrous  lactone 


or 


-OOC 

o -Phenolphthalein        Anhydride 


PHTHALEIN  DYES 


759 


(C) 


Pyronine 

The  o-phenolphthalein  of  the  lactone  formula  with  two  phenol 
hydroxyls  Bear  to  each  other  would  lose  water  and  the  resulting 
anhydride  if  written  as  in  (C)  is  plainly  a  pyronine  as  well  as  tri-phenyl 
methane  derivative  as  in  (B)  .  In  this  pyronine  structure,  however,  there 
is  no  quinoid  group  and  to  form  such  a  structure  by  the  conversion  of 
the  phenolphthalein  into  the  sodium  salt  does  not  appear  possible. 

Fluorescein 

In  a  related  phthalein  dye,  however,  this  condition  is  fully  met.  The 
dye  fluorescein  is  resorcinol  phthalein  and  is  made  from  phthalic  an- 
hydride or  phthalyl  chloride  and  resorcinol  just  as  phenol  phthalein  is 
made  from  phthalic  anhydride  and  phenol  (p.  750).  These  relation- 
ships may  be  expressed  as  follows  writing  the  final  dye  salt  both  as  a 
tri-phenyl  methane  derivative  (B)  and  as  a  pyronine  (C).  The  reac- 
tions are  exactly  analogous  to  those  given  for  the  preparation  of  phenol- 
phthalein and  its  dye  salt  (p.  750),  some  of  the  intermediate  steps  being 
omitted  in  the  present  case. 

OH(2) 

OH(4) 
OH(2) 


O 


+  H-C6H 


C6H 


•O 

C 
O 

Phthalicl 
anhydride 


OH(2) 

H(4) 

/OH(2) 
H— C6H3<( 

XOH(4) 

Resorcinol 

m-Di-hydroxy 

benzene 


C6H, 


C— C6H3< 

X0 


C 
O 

Resorcinol  phthalein 
Fluorescein 


760 


c— 


ORGANIC  CHEMISTRY 

Fiuorescein 


-OH 


-H— OH   CL/  \_OH  +NaOH 

\         /  ^° 


-ooc 


-ooc 

Hydrous  lactone  Anhydride  lactone 

Tri-phenyl  methane  formulas 

(C) 


NaO 


NaOOC 

Quinoid  dye^salt 


Dye  salt 
Pyronine  formula 


PHTHALEIN  DYES 


76i 


Uranine. — Phenolphthalein  is  a  yellow  crystalline  compound,  m.p. 
250°.  It  is  practically  insoluble  in  water  but  is  readily  soluble  in  alco- 
hol in  which  form  it  is  used  as  an  indicator.  Fluorescein  is  a  dark  red 
crystalline  compound,  practically  insoluble  in  water  but  soluble  in 
alcohol.  Its  sodium  salt  is  red  in  color  but  in  dilute  solution  exhibits  a 
remarkable  green  and  yellow  fluorescence,  hence  the  name  fluorescein. 
The  salt  is  known  as  uranine.  It  is  not  used  as  a  dye  by  itself  because 
of  its  faint  character  but  is  used  to  mix  with  others  in  order  to  impart 
fluorescence.  The  rhodamines  also  possess  fluorescent  properties 
mostly  blue  and  red. 

Eosine 

A  derivative  of  fluorescein  is  important  as  a  dye.  It  is  known  as 
cosine  from  the  Greek  word  for  dawn  because  its  color  is  a  fluorescent 
rose  like  the  color  of  the  sky  at  dawn.  It  is  used  as  a  silk  dye.  It  is 
the  tetra-bromine  derivative  of  fluorescein  potassium  salt. 


Br 


Eos 


The  preceding  discussion  of  the  tri-phenyl  methane  and  pyronine 
dyes  is  by  no  means  exhaustive  but  enough  has  been  said  to  give  the 
student  some  idea  of  the  importance  of  the  dye  compounds  which  are 
derived  from  the  hydrocarbon  tri-phenyl  methane;  also  to  give  the 
principal  facts  in  connection  with  their  relation  to  the  history  of  syn- 
thetic dyes  and  to  the  question  of  chemical  constitution  and  color  of 

dyestuffs. 

This  discussion  of  the  constitution  of  phenolphthalein  and  fluores- 
cein involves  the  work  of  numerous  investigators.  Among  these  we 


762  ORGANIC  CHEMISTRY 

may  mention    the  following:  von  Baeyer,  Bernthsen,  Friedlander, 
Herzig,  R.  Meyer,  O.  Fischer,  Green  and  Perkin,  Acree,  Ostwald. 

Tri-phenyl  Methyl 

Before  leaving  the  general  subject  of  tri-phenyl  methane  mention 
should  be  made  of  a  compound  recently  discovered  and  investigated 
principally  by  Gomberg.  This  compound  is  tri-phenyl  methyl 
(C6H5)3  =  C.  The  importance  of  the  compound  is  that  it  is  a 
case  of  a  compound  containing  a  tri-valent  carbon  atom.  In  other 
words  it  is  a  derivative  of  the  free  radical  methyl  (CH3).  A  dis- 
cussion of  this  compound  in  any  detail  would  involve  many  new 
ideas,  especially  concerning  the  existence  of  compounds  in  equilibrium 
with  each  other;  and  as  such  a  study  is  beyond  the  province  of  this 
text  it  will  not  be  entered  into.  We  may  simply  add  that  on  account 
of  the  importance  of  his  investigations  on  this  compound  and  the 
general  question  of  tri-valent  carbon  Gomberg  was  awarded  the 
Nichols  medal  in  1914. 

Di-benzyl,  Stilbene,  Tolane 

In  making  di-phenyl  methane  benzyl  chloride  reacts  with  phenyl 
chloride  in  the  presence  of  sodium. 

C6H5— CH2— (Cl  +  Na2  +  Cl)— C6H5   >   C6H6— CH2— C6H5 

Benzyl  chloride  Phenyl  chloride  Di-phenyl  methane 

When,  however,  benzyl  chloride  alone  is  treated  with  sodium  we  ob- 
tain a  compound  known  as  di-benzyl. 

C  6H  5— CH2— (Cl  +  Na2  +  Cl)— CH2— C  6H  6        > 

BTsoCd?umde  C6H6-CH2-CH2— C6H5  +  2NaCl 

Di-benzyl 
Sym.  Di-phenyl  ethane 

Di-benzyl  is  therefore  symmetrical  di-phenyl  ethane  as  is  also  proven 
by  its  preparation  from  symmetrical  di-chlor  ethane,  by  the  Friedel- 
Craf t  reaction,  with  benzene  as  f ollaws : 


C6H5— (H  +  C1)CH2— CH2— (Cl  +  H)— C6H5     ^_ 

Benzene  Ethylene  chloride  Benzene 

Sym.  Di-chlor  ethane 

CgHs — CH2 — CH2 — 

Di-benzyl 
Sym.  Di-phenyl  ethane 


DI-BENZYL     BENZOIN     BENZIL  763 

The  reaction  of  benzyl  chloride  with  sodium  also  takes  place  with 
benzal  chloride  and  sodium  yielding  an  ethylene  unsaturated  compound 
corresponding  to  di-benzyl. 

C6H5—  CH=  (C12  +  4Na  +  C12)  =  CH—  C6H5        —  > 

Benzal  chloride 
+  Sodium 

C6H5—  CH  =  CH—  C6H5  +  4NaCl 

Stillbene 
Sym.  Di-phenyl  ethene 

This  compound  which  is  sym.  di-phenyl  ethene  is  known  as  stil- 
bene.  Two  other  syntheses  of  stilbene  are  interesting.  When  ben- 
zaldehyde  is  distilled  over  sodium  two  molecules  lose  oxygen  and  the 
benzal  radicals  unite. 

C6H5—  CH=  (O  +  4Na  +  O)  =  CH—  C6H5        --  > 

Benzaldehyde  Benzaldehyde 

C6H5—  CH  =  CH—  C6H5 

Stilbene 

Also  when  the  vapor  of  toluene  is  passed  over  heated  lead  oxide  stilbene 
C6H5—  CH3  +  PbO  +  H3C—  C6H5  -  >  C6H5—  CH  =  CH—  C6H6 

Toluene  Toluene  Stilbene 

results.  From  stilbene  by  means  of  the  addition  of  bromine  and  sub- 
sequent loss  of  hydrogen  bromide,  by  treatment  with  alcoholic  pot 
assium  hydroxide  the  corresponding  acetylene  triple  bond  compound  is 
obtained.  This  is  known  as  tolane. 


=  CH—  C6H5  +  2Br        -  > 

Stilbene 
Di-phenyl  ethene 

(—  2HBr) 
C6H6—  CHBr—  CHBr—  C6H5         -*      C6H5—  C  =  C—  C6H6 

C4-KOH)  Tolane 

Di-phenyl  ethine 

Stilbene  is  important  in  connection  with  the  constitution  of  phenan- 
threne  (p.  807)  and  amino  derivatives  of  stilbene  yield  dyes. 

Benzoin.    Benzil 

Two  derivatives  of  di-benzyl  should  be  mentioned,  viz.,  benzoin 
and  benzil. 

C6H6—  CH2—  CH2—  C6H5  Di-benzyl 

C6H5—  CO—  CH(OH)—  C6H6        Benzoin 
C6H6—  CO—  CO—  C6H6  Benzil 


764  ORGANIC  CHEMISTRY 

Benzoin  is  formed  by  the  condensation  of  benzaldehyde  with  itself 
when  heated  with  potassium  cyanide.  This  is  analogous  to  the  aldol 
condensation  (p.  169). 


C6H5— CH  +  CH— C6H5    izr;  '    C6H6— C— CH— C6H5 

II  II  II      I 

O         O  O     OH 

Benzaldehyde  Benzoin 

This  compound  is  a  mixed  alcohol-ketone  compound.  When  oxidized 
with  nitric  acid  or  chlorine  the  alcoholic  group  is  converted  into  a 
ketone  group  and  a  de-ketone  known  as  benzil  is  obtained. 

C6H5— CO— CH(OH)— C6H5   —->    C6H5— CO— CO— C6H5 

Benzoin  Benzil 

Benzil  is  also  obtained  when  benzoyl  chloride  is  treated  with  sodium 
amalgam. 

C6H5— CO— (Cl  +  Na2  Cl)— CO— C6H5 >  C6H5— CO— CO— C6H5 

Benzoyl  chloride  Benzil 

Benzoin  being  an  alcohol-ketone  similar  to  carbohydrates  yields  osa- 
zones,  and  both  benzoin  and  benzil  as  ketones  yield  oximes.  The  di- 
oxime  of  benzil  exists  in  three  stereo-isomeric  forms. 

C6H5— C— C— C6H5   CCH5— C -C— C6H5 

II      II  II  II 

HO— N    N— OH  N— OH    HO— N 

anti-  Syn- 

f~*     TT    {** /"« /"»     TT 

II  II 

N— OH  N— OH 

amphi- 
Benzii  di-oximes 


3.  CONDENSED  RING  COMPOUNDS 

We  come  now  to  a  third  series  of  aromatic  hydrocarbons,  termed 
condensed  ring  compounds.  They  are  composed,  not  of  a  single  ring, 
as  are  benzene  and  its  homologues,  nor  of  two  or  more  rings  linked 
together,  usually  with  an  intervening  carbon  group,  as  in  di-phenyl 
and  related  compounds,  but  of  two  or  more  rings  condensed  together. 
Just  what  is  meant  by  this  term  condensed  rings  will  be  understood 
when  we  establish  the  constitution.  Three  important  hydrocarbons 
of  this  series  are  known,  viz.,  naphthalene,  anthracene  and  phenan- 
threne.  All  of  these  three  hydrocarbons  yield  derivatives  of  the  same 
classes  as  those  derived  from  benzene  and  many  of  them,  especially  those 
of  the  first  two  hydrocarbons,  are  of  particular  importance  as  dyes. 
Each  hydrocarbon  with  its  derivatives  will  be  considered  in  turn. 

NAPHTHALENE  AND  DERIVATIVES 


Naphthalene,  Ci0H8, 


Coal  Tar  Source. — Naphthalene  is  the  common  substance  used  in 
place  of  camphor  and  known  as  moth  balls.  It  is  obtained  from  coal 
tar  and  is  present  in  illuminating  gas  being  often  found  as  a  crystal- 
line deposit  in  the  gas  mains.  It  is  present  in  coal  tar  more  abundantly 
than  any  other  individual  compound,  the  yield  being  about  6.0-10.0 
per  cent.  Most  of  the  naphthalene  is  present  in  the  second  fraction 
or  middle  oil  obtained  from  the  first  fractional  distillation  of  coal  tar, 
i.e.,  the  fraction  distilling  between  lyo^o0.  This  is  redistilled  and 
the  crude  napthalene  is  collected  in  large  cooling  tanks  where  it  forms  a 
beautiful  crystalline  deposit.  The  adhering  oil  is  removed  by  means  of 
a  heated  hydraulic  press  and  the  thus  partially  purified  product  is 
treated  with  acids  and  alkalies  and  again  distilled  through  a  rectifying 
still.  The  product  so  obtained  is  about  90-95  per  cent  pure  and  may  be 
still  further  purified  by  sublimation.  Naphthalene  when  pure  crystal- 

765 


766  ORGANIC  CHEMISTRY 

lizes  in  shining  flakes,  m.p.  79.6°,  b.p.  218°.  It  is  insoluble  in  water 
but  distils  with  steam.  It  sublimes  when  heated  and  volatilizes  even 
at  ordinary  temperatures.  It  is  soluble  in  ether  and  in  hot  alcohol. 

Naphthalene  as  such  has  several  important  uses.  Its  most  common 
use  is  as  a  germicide  or  insecticide  against  the  attacks  of  the  moth  miller 
larvae  in  the  form  of  what  is  known  as  moth-balls.  A  more  important 
use  is  as  an  enricher  or  carburetter  of  water  gas  for  illuminating  pur- 
poses. As  it  contains  a  large  amount  of  carbon  it  burns  with  a  very 
luminous  flame  and  thus  makes  more  luminous  a  weakly  illuminating 
gas.  The  most  important  uses  of  all,  however,  are  as  a  source  of  ortho- 
phthalic  acid  and  in  yielding  derivatives  which  are  used  as  dyes. 

The  commercial  method  of  preparing  ortho-phth&lic  acid  is  from 
naphthalene  and  the  cheapness  of  this  process  has  been  essential,  as 
we  have  previously  stated,  to  the  commercial  synthesis  of  indigo  (p.  880) . 
The  method  originally  used  was  to  convert  naphthalene  into  its  tetra- 
chloride  and  then  oxidize  this  (p.  771).  Recently  the  process  consists  in 
the  oxidation  of  naphthalene. with  fuming  sulphuric  acid  in  presence 
of  mercury  salts  or  salts  of  rare  earths  which  act  as  catalyzers.  The 
oxidation  takes  place  with  the  oxygen  of  the  air,  the  mercury  and 
sulphuric  acid  being  entirely  recovered.  An  electrolytic  process  by 
which  naphthalene  becomes  oxidized  to  phthalic  acid  and  naphtho- 
quinone  has  also  been  used.  The  reactions  of  these  processes  so  far  as 
the  naphthalene  is  concerned  will  be  discussed  now  in  connection  with 
the  study  of  its  constitution.  An  indirect  process  for  converting 
naphthalene  into  phthalic  acid  is  through  the  hydroxyl  derivatives 
or  naphthols  (p.  783),  by  fusion  with  potassium  hydroxide  in  presence 
of  metal  oxides. 

Constitution. — The  composition  of  naphthalene  is  represented  by 
the  formula  CioH8.  What  is  its  constitution?  In  the  first  place  it  is 
a  hydrocarbon  similar  in  its  chemical  properties  to  benzene  and  not  to 
methane.  It  readily  forms  nitro  and  sulphonic  acid  derivatives  and  its 
hydroxyl  derivatives  are  analogous  to  phenols,  not  to  alcohols.  It  also 
yields  hydrogen  and  halogen  addition  products  like  benzene.  The 
true  constitution  of  the  compound  has  been  established  by  reactions 
both  of  decomposition  and  of  synthesis. 

Yields  ortho-Phthalic  Acid. — The  simplest  proof  that  naphthalene 
does  contain  a  benzene  ring  is  found  in  the  fact  that  on  oxidation  it  yields 
phthalic  acid  and  always  the  ortho  compound.  This  would  indicate 


NAPHTHALENE  AND  DERIVATIVES  767 

that  in  naphthalene  there  must  be  present  a  benzene  ring  with  side  chain 
carbon  groups  linked  to  it  in  two  positions  ortho  to  each  other.  If,  in 
the  empirical  formula  CioH8,  we  allow  for  a  di-substituted  benzene  ring, 
i.e.,  C6H4,  we  shall  have  left  a  group,  C4H4,  and  the  formula  for  naph- 
thalene may  be  written  C6H4  =  C4H4.  As  the  group  C4H4  is  linked 
to  the  ring  in  two  positions  the  simplest  and  practically  the  only  way 
in  which  we  may  consider  it  is  as  four  CH  groups  linked  together  so 
as  to  satisfy  the  tetra-valence  of  carbon.  The  formula  and  above  re- 
action may  then  be  represented. 

CH  =  CH  COOH(i) 

r'w/  f  u 


COOH(2) 

Naphthalene  o-Phthalic  acid 

The  easy  oxidation  of  such  unsaturated  side  chains  would  be  expected 
(p.  670). 

Synthesis  from  Phenyl  Butylene  Bromide.  —  That  this  must  repre- 
sent the  constitution,  at  least  in  part,  is  proven  by  the  synthesis  of 
naphthalene  from  phenyl  butylene  bromide.  When  4-phenyl  AI- 
butene,  i.e.,  C6H5—  CH2—  CH2—  CH  =  CH2  (p.  158),  is  treated  with 
bromine  two  atoms  of  the  halogen  add  on  to  the  double  linked  carbons 
giving  phenyl  butylene  bromide,  C6H6—  CH2—  CH2—  CHBr—  CH2Br, 
i-2-di-brom  4-phenyl  butane.  This  compound  on  heating  loses  two 
molecules  of  hydrogen  bromide  and  also  two  atoms  of  hydrogen  and  the 
product  is  naphthalene.  From  what  has  been  previously  proven  this 
reaction  must  result  in  linking  the  aliphatic  side  chain  at  a  second  point 
in  the  benzene  ring  ortho  to  the  one  already  held.  The  reaction  is, 
therefore, 

H  H 

°  (H)     (H) 

C  ---  CH—  CH  HCr  c—  CH  =  CH 


O  , 

C  ---  CH—  CH  HCr^       N 

C    (Br)CH-CH  HcL  J 

H  H      Br  ^ 


c-CH 


H  (-2H)  (-2HBr)  H 

Phenyl  butylene  bromide  Naphthalene 

i-2-Di-brom     4-phenyl  butane 

It  should  be  emphasized  also  that  in  phenyl  butylene  bromide  we  have 
a  space  relationship  exactly  the  same  as  in  the  case  of  an  epsilon- 


y68 


ORGANIC  CHEMISTRY 


hydroxy  acid  which,  like  the  gamma-  and  delta-adds.,  readily  loses 
water  yielding  a  lactone  anhydride  (p.  242).  The  ortho  carbon  of  the 
ring  and  the  end  carbon  of  the  butane  side  chain  are  the  ends  of  a  six 
carbon  chain  so  that  the  bromine  linked  to  one  and  the  hydrogen  linked 
to  the  other  are  in  very  close  proximity.  Hydrobromic  acid,  HBr,  is 
therefore  easily  lost  and  the  end  of  the  side  chain  becomes  linked  to  the 
ortho  carbon  of  the  ring.  As  in  similar  cases  this  is  clearly  seen  if  tetra- 
hedral  models  are  used. 

From  Phenyl  Vinyl  Acetic  Acid. — A  second  synthesis  very  closely 
analogous  to  the  preceding  is  from  phenyl  vinyl  acetic  acid  (p.  700), 
which  has  the  constitution  C6H5— CH  =  CH— CH2— COOH.  When 
this  is  heated  it  loses  water  and  yields  a  hydroxy  naphthalene  or  naph- 
thol  in  which  the  hydroxyl  is  linked  to  the  carbon  next  to  the  ortho 
carbon  of  the  ring. 

H 

C 


HC 
HC 


CH=CH 


O-H— OH 
C(H        HO)— C— CH 


CH 


C 
H 

Phenyl  vinyl  acetic  acid 


HC 

C 
H 

Hydroxy  naphthalene 

From    Tetra-carboxy    Ethane. — i-i-2-2-Tetra-carboxy    ethane 

which  may  be  prepared  as  the  tetra'-ethyl  ester  by  the  malonic 
ester  synthesis  (p.  276),  yields  a  di-sodium  compound  analogous  to  the 
mono-sodium  compound  of  malonic  ester.  This  compound  is  (C2H5- 
OOC)2  =  CNa— NaC  =  (COOC2H5)2.  Now  when  this  compound  re- 

/CH2Br  (i) 


acts  with  ortho-di-(brom -methyl)  benzene,  G6H4<f  ,  which 

XCH2Br  (2) 
is  made  from  ortho-xylene,  two  molecules  of  sodium  bromide  are 


.     NAPHTHALENE  AND  DERIVATIVES  769 

eliminated  and  after  hydrolysis  of  the  resulting  ester  and  loss  of  four 
molecules  of  carbon  dioxide  from  the  resulting  acid  the  final  product  is 
a  tetra-hydrogen  addition  product  of  naphthalene.  The  reactions  are, 

CH2—  (Br  (i)        Na)—  C  =  (COOC2H5)2 
C6H/  +  |  _> 

XCH2—  (Br  (2)        Na)—  C  =  (COOC2H5)2 

o-Di-(brom-methyl)  Di-sodium  tetra-carboxy 

benzene  ethane,  tetra-ethyl  ester 

/CH2-C=(COOC2H5)2 
C6H/  |  f  155 

XCH2—  C  =  (COOC2H5)2 

d)  d) 

yCH2-C  =  (COOH)2  CH2-CH 

/ 


y 
-    C6H  |  ^°*)      C6H/ 

XCH2—  C  =  (COOH)2  XCH2—  CH2 

(2)  (2) 

Tetra-hydro  naphthalene 

Thus  the  constitution  of  naphthalene  must  be  represented  as  a  benzene 
ring  linked  in  two  positions  ortho  to  each  other  to  the  unsaturated  group, 

—  CH  =  CH 

I      . 

—  CH  =  CH 

Two  Benzene  Rings.  Erlenmeyer.  Graebe.  —  The  work  of  Graebe 
on  the  oxidation  products  of  nitro  naphthalene  and  amino  naphthalene 
throws  yet  more  light  upon  this  constitution  and  sustains  an  idea  first 
suggested  by  Erlenmeyer  that  naphthalene  contains  not  one  benzene 
ring  only  but  two  such  rings  condensed  together.  We  have  said  that 
naphthalene  on  oxidation  yields  phthalic  acid.  Now  by  substituting  a 
nitro  group  in  naphthalene  nitro  naphthalene  is  obtained.  This 
nitro  naphthalene  is  easily  reduced  to  amino  naphthalene  with  the 
amino  group  evidently  occupying  the  same  position  as  the  nitro  group. 
Now  it  is  a  striking  fact  that  on  oxidation  the  nitro  naphthalene  yields 
nitro  ortho  -phthalic  acid  but  the  amino  naphthalene  yields  ortho- 
phthalic  acid,  without  any  substituting  group  in  the  benzene  ring  other 
than  the  carboxyls.  In  one  case  the  nucleus  of  naphthalene  which 
contains  the  nitro  group  remains  as  a  benzene  ring  in  nitro  phthalic  acid 
while  in  the  other  case  the  nucleus  of  naphthalene  which  contains  the 
amino  group,  which  must  be  the  benzene  ring  of  nitro  naphthalene  and 
nitro  phthalic  acid,  is  destroyed,  yet  there  remains  an  unsubstituted 

49 


ORGANIC  CHEMISTRY 


benzene  ring  in  the  phthalic  acid.  Therefore  in  naphthalene  there  must 
be  two  benzene  rings,  or  better,  two  parts  either  one  of  which  remains  as 
a  benzene  ring  on  the  oxidation  of  the  other  part  to  two  carboxyls. 
If  the  formula  for  naphthalene  as  we  have  written  it  be  built  up  of 
tetra-hedral  models  we  shall  find  that  the  two  halves  are  exactly  alike 
and  our  formula  should  be  written  not 

H 


CH 
HCV"         >C— CH  =  CH 


:Q 


but 


C— CH  =  CH 


HC 


CH 


H  H 

Naphthalene 

That  is,  there  are  two  benzene  rings  condensed  together  by  two  carbons 
in  common  so  that  either  one  is  a  complete  ring.  The  reactions  of  nitro 
naphthalene  and  amino  naphthalene,  may  be  represented  as  follows: 

H  H  H 

C  C  C 

C— COOH      % 
C— COOH 


NO2 

Nitro  phthalic  acid 

H 
C 


+o 


HOOC—  C 
HOOC—  c 


H2N 

Amino  naphthalene 


C 
H 

Phthalic  acid 


NAPHTHALENE  AND  DERIVATIVES 


771 


Either  one  of  the  nuclei!  indicated  by  i  and  2  remains  as  a  complete 
benzene  ring  in  the  products  the  other  ring  being  destroyed.  It  is 
not  really  two  benzene  rings  but,  as  it  were,  two  such  rings  condensed 
in  such  a  way  that  two  carbon  atoms  are  in  common,  so  that  while 
only  one  complete  ring  exists  either  part  of  the  compound  may  be  this 
ring. 

Chlor  Naphthalenes. — Another  series  of  reactions  which  support  the 
view  just  discussed,  that  in  naphthalene  there  are  present  two  nuclei 
either  one  of  which  is  a  benzene  ring,  is  found  in  Laurent's  work  on  the 
chlorine  substitution  products  of  naphthalene.  When  naphthalene  is 
chlorinated  it  yields  different  chlor  naphthalenes.  Two  of  these  are 
important  in  this  place,  viz.,  a  tetra-chlor  naphthalene,  CioH4Cl4  and 
a  penta-chlor  naphthalene,  CioHaCU.  Now  the  first  one  must  have  all 
four  chlorines  linked  to  one  nucleus  because  on  oxidation  it  yields 
ortho-phthalic  acid,  as  below.  The  penta-chlor  compound  must  of 
necessity  have  at  least  one  of  the  chlorines  linked  to  the  second  nucleus 
as  only  four  are  possible  of  being  linked  to  one  nucleus.  Now  this 
compound  on  oxidation  yields  not  mono-chlor  phthalic  acid  but  tetra- 
chlor  phthalic  acid.  The  reactions  may  be  represented  as  follows: 


4HC1 


II 

C 


+0 


OC— COOH 
C— COOH 


Tetra-chlor  naphthalene 


C 
H 

o-Phthalic  acid 


772  ORGANIC  CHEMISTRY 


Cl 
C 


-4-M       HOOC— ( 

5HC1  + 

JCC1  HOOC— Ck         ^CCl 


^ 


C 
Cl 

Penta-chlor  naphthalene  Tetra-chlor 

o-phthalic  acid 


In  the  first  case  one  nucleus  remains  as  a  benzene  ring  in  phthalic  acid 
while  in  the  second  case  it  must  be  the  other  nucleus  which  remains  as 
a  benzene  ring  in  tetra-chlor  phthalic  acid.  The  proof  here  then  is 
exactly  the  same  as  in  the  case  of  nitro  naphthalene  and  amino  naph- 
thalene, viz.,  that  in  naphthalene  either  nucleus  is  a  benzene  ring. 

Tetra-hydro  Naphthylamines. — That  at  one  time  only  one  ben- 
zene ring  is  actually  present  in  naphthalene  is  shown  by  the  work 
of  Bamberger  on  the  tetra-hydro  naphthylamines.  Mono-amino 
naphthalenes,  analogous  to  aniline,  are  called  naphthylamines. 
These  naphthylamines  yield  hydrogen  addition  products  analogous 
to  those  formed  from  benzene  (p.  811)  or  naphthalene.  Now  one 
of  the  naphthylamines,  viz.,  alpha -naphthylamine  (the  isomerism 
will  be  discussed  presently,  (p.  775),  yields  two  different  products  by 
the  addition  of  four  hydrogen  atoms.  That  these  two  compounds 
are  different  and  that  the  addition  of  four  hydrogen  atoms  distinctly 
changes  the  character  of  the  nucleus  to  which  they  are  added  is 
seen  from  the  following  reactions. 


HC 


NAPHTHALENE  AND  DERIVATIVES 
NH2 

H2 

C 


77.3 


NH2 

I 
C 


+0 


H 


H  H 

a-N.ph.hy.amine 


C 

H  W 

TeL-hydro 
a-naphthylamine 

(aromatic) 


or 


Adipic  acid,  i-4-Di-carboxy  butane 

NH2 


+0 


c         c 

^r          ^         ^XX' 

C             C 

H             H 

H             Ho 

a-Naphthylamine 

•*-                       ^-*-2 
Tetra-hydro 

H 

a-naphthylamine 

(alicyclic) 

H 

C 

^tw 

C 

C 

)H    +Q     HC^^C-COOR 

Hcl^Jc—  COOH 
C 

H 

H 

>xy  /9-phenyl 

lion  ir  a/Mri 

o-Phthalic 

acid 


774  ORGANIC  CHEMISTRY 

When  alpha-naphthylamine,  in  amyl  alcohol,  is  treated  with  sodium 
amalgam  four  hydrogens  are  added  to  the  naphthyl  amine.  The  tetra- 
hydro  naphthylamine  obtained  must  have  the  four  hydrogens  added 
to  the  other  nucleus  than  the  one  to  which  the  amino  group  is  linked 
because  on  oxidation  an  aliphatic  di-basic  acid  is  obtained  containing 
four  CH2  groups  and  the  amino  group  with  the  nucleus  to  which  it 
was  linked  is  destroyed  yielding  the  two  carboxyl  groups.  That  this 
latter  nucleus  is  a  benzene  ring  is  indicated  by  the  fact  that  the  tetra- 
hydro  naphthylamine  possesses  properties  like  an  aromatic  amine, 
aniline,  and  not  like  an  aliphatic  amine,  methyl  amine,  e.g.,  it  readily 
undergoes  the  diazo  reaction  and  is  not  ammoniacal  in  odor.  On  this 
account  this  particular  tetrahydro  naphthylamine  and  others  similar 
to  it  are  termed  aromatic  tetra-hydro  naphthylamines.  It  will  be  seen 
that  the  addition  of  the  four  hydrogens  to  one  of  the  nucleii  makes  that 
nucleus  distinctly  saturated  or  aliphatic  in  character  as  is  shown  by 
the  formula  and  by  the  aliphatic  acid  resulting  from  oxidation.  That 
is,  the  addition  of  hydrogen  and  conversion  of  a  nucleus  into  a  saturated 
ring  makes  it  impossible  for  this  nucleus  to  remain  as  a  benzene  ring 
when  the  other  nucleus  is  destroyed.  Thus  only  one  nucleus  is  a  ben- 
zene ring  at  any  one  time.  That  one  of  the  two  nucleii,  and  this  may 
be  either  of  the  two,  is  a  benzene  ring  has  already  been  proven  by  the 
oxidation  products  of  nitro  naphthalene  and  amino  naphthalene  (p. 
770)  and  is  further  proven  by  the  second  reaction  above.  The  nucleus, 
which,  in  the  first  reaction,  loses  its  benzene  ring  properties  and  yields 
an  aliphatic  acid,  in  the  second  reaction  retains  its  benzene  properties 
and  yields  an  aromatic  acid,  orthophthalic  acid.  Also  the  nucleus  con- 
taining the  amino  group  is  aromatic  in  the  tetra-hydro  compound  in 
the  first  reaction  but  becomes  alicyclic  in  the  isomeric  compound  in 
the  second  reaction,  yielding  on  oxidation  a  three  carbon  aliphatic 
chain  in  ortho-carboxy  jS-phenyl  propionic  acid  (p.  697).  The  ali- 
phatic character  of  the  nucleus  to  which  the  amino  group  is  linked  in 
the  second  tetra-hydro  product  is  shown  by  the  fact  that  this  compound 
is  like  aliphatic  amines  in  character,  i.e.,  it  is  strongly  ammoniacal  in 
odor  and  does  not  undergo  diazotization.  It  is  termed  an  alicyclic 
tetra-hydro  naphthylamine. 

Thus  the  final  conclusion  in  regard  to  the  constitution  of  naphtha- 
lene is  that  it  consists  of  one  benzene  ring  with  a  four  carbon  chain  of 
(CH)  groups  linked  by  its  two  end  carbons  to  the  ring  in  two  positions 


NAPHTHALENE  AND  DERIVATIVES 


775 


ortho  to  each  other.  As  such  a  structure  is  symmetrical  either  part 
may  be  considered  as  the  ring  and  the  other  as  constituting  the  four 
carbon  chain.  Either  nucleus  may  in  fact  remain  as  a 'benzene  ring 
on  the  destruction  of  the  other,  but  if,  by  the  addition  of  hydrogen,  the 
character  of  either  nucleus  is  changed  to  that  of  a  saturated  ring  it 
thus  loses  its  benzene  character  and  cannot  remain  as  a  benzene  ring, 
the  other  nucleus,  however,  retaining  its  character  as  a  true  benzene 
ring.  As  the  structure  has  the  appearance  of  two  benzene  rings  with 
one  side  of  two  carbon  atoms  in  common  it  is  usually  referred  to  as  a 
condensed  benzene  ring  compound,  i.e.,  two  benzene  rings  condensed 
together  into  one  compound. 

DERIVATIVES 

Isomerism. — From  the  condensed  ring  structure  of  naphthalene  we 
should  expect  at  least  as  great  possibility  of  isomerism  in  its  derivatives 
as  was  found  in  the  case  of  derivatives  of  benzene.  The  fact  is  that 
the  possibility  of  isomerism  is  much  greater.  As  was  done  in  the  case 
of  the  single  benzene  ring  we  may  arbitrarily  number  the  positions  in  the 
naphthalene  formula.  The  numbering  generally  accepted  is  as  follows: 
H  H 

C 

Naphthalene 


C      I0      C 

H  H 

It  will  be  observed  that  substitution  or  addition  may  take  place  in 
any  or  all  of  the  positions  i,  2,  3,  4,  5,  6,  7,  8,  while  in  positions  9  and 
10  addition  only  is  possible. 

Mono-substitution  Products,  alpha  and  beta. — In  the  benzene  ring 
we  found  that  no  isomeric  mono-substitution  products  are  known  and 
according  to  the  hexagon  formula  none  are  possible.  With  naphthalene, 
however,  two  isomeric  mono-substitution  products  are  known  in  all  classes 
of  derivatives.  Examination  of  the  formula  shows  that  this  is  possible. 
Positions  i,  4,  5,  8  are  alike  and  when  substitution  in  one  of  these  posi- 
tions takes  place  the  product  is  designated  as  an  alpha  compound. 
These  four  positions  are  different  from  the  remaining  four,  viz.,  2,  3,  6, 


776  ORGANIC  CHEMISTRY 

7,  which  are  also  alike  and  which  are  designated  as  the  beta  positions. 
In  case  there  is  a  second  substituting  group,  and  the  terms  alpha  and 
beta  are  used,  the  four  positions  in  each  set  are  also  numbered  as  follows: 


Di-substitution  Products. — Usually  however  the  di-substitution 
products  are  designated  by  numbers  as  first  indicated.  The  names 
ortho,  meta  and  para  are  also  sometimes  used  exactly  as  in  the  benzene 
products  together  with  other  similar  names  applying  to  definite  pairs 
of  positions.  By  examining  the  formula  we  shall  find  that  ten  isomeric 
di-substitution  products  of  naphthalene  are  possible  in  case  the  two 
substituents  are  the  same.  These  ten  with  their  numerical  designa- 
tions and  names  are  as  follows; 

(1)  1-2  or  cti-&\;  (3-4  or  ^2-^2;  5-6  or  az-fis;  7-8  or  (3  4-014)  are  all  ortho 

(2)  2-3  or  /3i-/32;  (6-7  or  ps-pt)  are  also  ortho 

(3)  i~3  °r  ai~Pz>  (2~4  °r  ffi~«2;  5-7  or  ay-p^  6-8  or  $3-014)  are  all  meta 

(4)  1-4  or  oii-az\  (5~8  °r  «s~«4)  are  para 

(5)  1-8  or  oti-on;  (4-5  or  a2-a3)  are  peri 

(6)  1-5  or  ar-«3;  (4-8  or  a2-a4)  are  ana 

(7)  1-6  or  on- fa;  (4-7  or  a2-/34;  2-5  or  ffi-«3;  3-8  or  £2-a4)  are  epi 

(8)  1-7  or  ai-p4]  (4-6  or  «2-/33;  3-5  or  02-<*3;  2-8  or  fa-en)  are  kata 

(9)  2-6  or  fa-fa;  (3-7  or  j32-j34)  are  amphi 
(10)  2-7  or  fa- fa;  (3-6  or  ftr-08)  are  />ro^ 

In  case  the  two  substituents  are  different  four  additional  isomers  are 
possible,  as  indicated  by  the  underscored  pairs  of  positions,  making 
a  total  of  fourteen.  These  are  all  known  in  the  case  of  the  mixed  amine 
and  sulphonic  acid  naphthalenes  (p.  786).  We  may  simply  state  that 
in  case  like  substituents  enter  the  naphthalene  the  possibilities  are: 

tri-substituted  naphthalenes 14 

tetra-  substituted  naphthalenes 22 

penta -substituted   naphthalenes 14 

hexa-substituted  naphthalenes 10 

hepta-substituted  naphthalenes 2 

octa-substituted  naphthalenes i 


NAPHTHALENE  AND  DERIVATIVES 


777 


Thus  we  can  see  how  numerous  are  the  possible  isomers  among  the 
derivatives  of  naphthalene. 

Halogen  Derivatives 

Substitution  Products. — The  halogen  derivatives  of  naphthalene 
include  both  substitution  and  addition  products.  The  tetra-  and 
penta-chlor  substituted  naphthalenes  have  already  been  referred  to  as 
furnishing  proof  that  in  naphthalene  there  are  present  two  benzene 
nucleii  (p.  771).  Other  halogen  substituted  naphthalenes  are  known 
but  none  need  be  discussed  in  detail. 

Addition  Products. — The  halogen  addition  products  of  naphthalene 
«,re  more  easily  formed  than  are  the  substitution  products.  The  tetra- 
chlor  compound  is  of  special  interest  and  has  been  referred  to.  We 
have  stated  that  naphthalene  is  oxidized  to  0r//f0-phthalic  acid.  This 
oxidation  was  originally  carried  out  not  with  naphthalene  itself  but 
with  naphthalene  tetra-chloride,  CioH8Cl4.  When  naphthalene  is 
treated  with  chlorine  (potassium  chlorate,  KClOs  and  hydrochloric 
acid  HC1),  addition  takes  place  and  the  tetra-chlor  addition  product 
is  formed.  By  the  further  action  of  the  chlorine,  as  an  oxidizing  agent, 
the  tetra-chloride  is  converted  into  ortho-phthalic  acid. 

H  H 

C  C 


(KC103  +  HC1) 


CHC1 


CHC1 


+  0 


H 


C— COOH 


C— COOH 


C  CC1  C 

H  H  H 

Naphthalene  tetra-chloride  o-Phthalic  acid 

This  reaction  is  easily  carried  out  in  the  laboratory  and  is  a  common 


778 


ORGANIC  CHEMISTRY 


exercise.  For  a  long  time  it  was  the  commercial  method  of  converting 
naphthalene  into  phthalic  acid  but  it  has  been  replaced  by  the  oxida- 
tion of  naphthalene  with  sulphuric  acid  in  the  presence  of  a  catalytic 
salt  as  previously  stated  (p.  766). 

Nitro  Naphthalenes 

The  nitro  substitution  products  of  naphthalene  are  easily  prepared 
by  the  action  of  nitric  acid  on  the  hydrocarbon.  By  such  direct  nitra- 
tion the  product  obtained  is  alpha-nitro  naphthalene.  This  is  proven 
by  the  following  series  of  reactions.  Nitro -naphthalene  by  reduction 
yields  amino  naphthalene,  naphthylamine,  which  by  the  diazo  reaction 
yields  hydroxy  naphthalene,  naphthol.  Now  the  naphthol  so  obtained 
is  identical  with  the  one  resulting  from  the  phenyl  vinyl  acetic  acid 
synthesis  (p.  768)  and  this  must  be  the  alpha  compound. 


-H2O 


=  CH— CH— C(O)OH 

(H) 


C(H) 


C 
H 

Phenyl  vinyl 
acetic  acid 


NAPHTHALENE  AND  DERIVATIVES  779 

In  the  naphthalene  derivatives  the  identification  of  a  compound  as  an 
alpha  substitution  product  is  usually  accomplished  by  converting  it. 
into  one  of  the  compounds  above. 

Naphthylamines,  Amino  Naphthalenes 

Synthesis  from  Naphthols. — The  mono-ammo  substitution  products 
of  naphthalene  are  known  as  naphthylamines.  Two  such  compounds 
are  known,  viz.,  an  alpha  and  a  beta.  Each  may  be  prepared  by  the 
reduction  of  the  corresponding  nitro  naphthalene,  and  also  from  the 
corresponding  hydroxy  naphthalene  or  naphthol  by  treatment  with 
ammonio-zinc  chloride  or  ammonio- calcium  chloride.  These  two 
reagents  are  made  by  passing  ammonia  gas  over  anhydrous  zinc  chlo- 
ride or  anhydrous  calcium  chloride.  On  heating  they  each  yield  am- 
monia and  the  anhydrous  salt.  They  are  thus  common  reagents  for 
effecting  the  action  of  ammonia  at  high  temperatures  and  at  the  same 
time  causing  the  elimination  of  water  due  to  the  action  of  the  anhydrous 
zinc  or  calcium  chloride. 

•(OH  +  H)— NH2  (Ammonio- 
zinc  chloride) 


>Naphtho 


/3-Naphthylamine 

This  same  reaction  may  be  brought  about  by  heating  the  naphthol  with 
ammonium  chloride  and  sodium  hydroxide  in  an  autoclave  at  160°  for 
two  or  three  days.  This  formation  of  an  amino  derivative  from  a 
hydroxyl  derivative  by  means  of  ammonia  does  not  usually  take  place 
though  it  is  possible  to  make  aniline  from  phenol  in  this  way. 

alpha-Naphthylamine. — alpha-Naphthylamine  is  a  solid  melting  at 
50°.  It  usually  possesses  a  strong  fecal-like  odor  though  it  is  claimed 
to  be  odorless  when  pure.  The  salts  react  with  a  solution  of  ferric 
chloride  giving  a  blue  precipitate. 

beta-Naphthylamine.— beta-Naphthylamine  is  also  solid,  m.p.  112°, 
with  a  slight  odor.  Salts  of  this  amine  do  not  cause  any  precipitate 
with  solutions  of  ferric  chloride. 


y8o 


ORGANIC  CHEMISTRY 


Relation  to  Dyes. — The  importance  of  the  naphthylamines  is  due 
to  the  fact  that  they  are  intermediate  products  in  the  preparation  of 
many  valuable  dyes  especially  of  the  azo  dye  series. 

Diazotization. — Like  aniline  and  other  aromatic  primary  amines 
they  undergo  diazotization.  The  resulting  diazo  compounds  undergo 
the  various  diazo  reactions  (p.  60 1)  by  means  of  which  the  naphthalene 
group  becomes  coupled  as  an  azo  compound  with  other  naphthalene  or 
benzene  rings.  These  azo  compounds  are  dyes.  The  most  important 
dyes  of  this  group  are  derived  from  mixed  amino  and  sulphonic  acid 
or  mixed  amino  and  hydroxyl  derivatives  of  naphthalene  and  will  be 
considered  a  little  later.  Not  only,  however,  may  the  naphthylamines 
yield  diazo  compounds  and  through  them  azo  compounds  but  they 
may  be  coupled  as  azo  compounds  with  a  diazotized  benzene  compound. 

Reagent  for  Nitrites  in  Water. — An  illustration  of  such  a  reaction 
is  one  which  is  the  basis  of  the  colorimetric  determination  of  nitrites  in 
water.  When  sulphanilic  acid,  para-amino  benzene  sulphonic  acid,  is 
diazotized  and  the  resulting  diazo  compound  treated  with  alpha- 
naphthylamine  the  benzene  ring  and  the  naphthalene  ring  become 
coupled  as  an  azo  compound  which  is  red  in  color. 

SO2OH  SO2OH 


Diazotization 


O  =  N— OH  +  H2SO4)  N— (SO4H 


NH2( 

Sulphanilic  acid 
p-Amino  benzene 
sulphonic  acid 


NH2 


N 

p-Sulpho  benzene 
diazonium  sulphate 


SO2OH 


H) 

a-Naphthyl  amine 


p-Sulpho  benzene  azo-i-naphthyl 
amine-4 


NAPHTHALENE  AND  DERIVATIVES 


78l 


When  a  small  amount  of  nitrites  is  present  in  water  and  the  reagent 
of  mixed  sulphanilic  acid  and  alpha-naphthylamine  is  added  in  the 
presence  of  sulphuric  acid,  the  acid  first  reacts  with  the  nitrites  forming 
nitrous  acid.  The  above  diazo  reaction  and  the  coupling  with  the 
naphthylamine  then  take  place  slowly  with  the  production  of  a  red 
color  in  the  solution.  The  depth  of  the  color  thus  produced,  on  com- 
parison with  the  color  obtained  with  standard  nitrite  solutions,  gives 
the  means  for  calculating  the  amount  of  nitrites  in  the  original  water. 

Hydrated  Naphthylamines. — We  have  referred  to  the  hydrated 
naphthylamines  in  our  discussion  of  the  constitution  of  naphthalene 
(p.  772).  The  tetra-hydro  products  are  of  two  kinds:  (i)  Those 
termed  aromatic  in  which  the  hydrogen  is  added  to  the  benzene  nucleus 
which  does  not  contain  the  amino  group  and  which  possess  the 
characters  of  aromatic  amines.  (2)  Those  termed  alicyclic  in  which  the 
hydrogen  is  added  to  the  benzene  nucleus  which  does  contain  the  amino 
group  and  which  possess  the  characters  of  aliphatic  amines.  Now 
while  the  alpha-  and  Z>e/a-naphthylamines  each 'yield  both  kinds  of 
tetra-hydro  products  if  subjected  to  proper  treatment  yet  by  the  same 
treatment,  viz.,  with  sodium  amalgam  in  amyl  alcohol,  the  alpha- 
naphthylamine  yields  an  aromatic  tetra-hydro  compound  while  the 
foto-naphthylamine  yields  mostly  an  alicyclic  compound. 

NH2  NH2 

H  H2  | 

C  C  C  C 

C 


HC 


H2C 


CH 


aromatic  Tetra-hydro  a-naphthylamine 

H  H2 

C  C 


HC 


HC 


alicyclic  Tetra-  hydro 
0-naphthylamine 


782 


ORGANIC  CHEMISTRY 


Naphthalene  Sulphonic  Acids 

Naphthalene  like  benzene  is  readily  sulphonated  by  the  direct 
action  of  sulphuric  acid.  When  the  reaction  takes  place  at  moderate 
temperatures,  about  80°,  the  product  is  mostly  the  alpha  compound 
while  at  higher  temperatures,  about  160°,  the  beta  compound  is  formed, 
the  alpha-naphthalene  sulphonic  acid  being  transformed  into  its  beta 
isomer  at  this  temperature. 

H  (H 

C  C 


at  80 


H-  HO)—  S02—  OH 


ati6o 


HC 


CH 


C— S02OH 


sulphonic  acid 


sulphonic  acid 


Not  only  mono-sulphonic  acids  but  also  di-  and  tri-sulphonic  acids  are 
known.  These  all  undergo  the  general  reactions  of  the  class  as  dis- 
cussed under  the  sulphonic  acid  derivatives  of  benzene  (p.  519).  On 
fusion  with  potassium  hydroxide  they  yield  hydroxyl  derivatives  and 
similar  fusion  with  potassium  cyanide  converts  them  into  acid  nitriles. 
They  are  characterized  as  soluble  compounds  and  are  readily  coupled 
with  diazo  compounds  yielding  azo  compounds  many  of  which  are 
dyes. 

Naphthols,  Hydroxy  Naphthalenes 

The  hydroxy  naphthalenes  are  known  as  naphthols.    They  possess 
a  phenol-like  odor  and  are  exactly  analogous  to  the  phenols  both  in 


DYES  FROM  NAPHTHALENE  DERIVATIVES  783 

methods  of  preparation  and  in  properties.  The  hydroxyl  group,  how- 
ever, is  more  reactive  than  in  the  benzene  analogue.  When  fused  with 
potassium  hydroxide  together  with  a  metallic  oxide  the  naphthols  are 
oxidized  to  phthalic  acid  and  benzoic  acid. 

Synthesis  from  Naphthalene  Sulphonic  Acids.— The  simplest 
method  of  synthesis  is  from  the  corresponding  naphthalene  sulphonic 
acid  by  fusion  with  potassium  hydroxide. 

From  Naphthylamines.— They  may  also  be  prepared  from  the 
naphthylamines  by  diazotizing  the  amine  and  then  decomposing  the 
resulting  diazo  compound  with  water. 

(N2)-(C1+H)OH 


(diazo  tization) 


OH 


a-Naphthalene 
cliazonium  chloride 


a-Naphthol 

While  this  reaction  may  be  used  it  is  more  customary,  especially  in  the 
case  of  the  beta  compounds,  to  effect  the  reverse  result,  viz.,  to  prepare 
the  amine  from  the  hydroxyl  compound  by  the  action  of  ammonia  in 
the  form  of  ammonio-zinc  chloride  as  already  discussed  (p.  779). 

Dyes,  Orange  II. — The  naphthols  yield  important  derivatives  many 
of  which  are  valuable  as  dyes.  Most  of  the  naphthol  dyes  are  deriva- 
tives of  mixed  naphthol  sulphonic  aicd  or  nitro  naphthol  compounds. 
These  will  be  considered  later.  One  important  dye,  however,  is  an  azo 
derivative  of  foto-naphthol.  It  is  analogous  to  the  red  colored  com- 
pound formed  in  the  test  for  nitrites  in  water  (p.  780)  and  is  prepared 
by  treating  beta-naphthol  with  the  diazo  compound  of  sulphanilic  acid, 
para-amino  benzene  sulphonic  acid,  the  naphthol  being  coupled  to  the 
benzene  ring  as  an  azo  compound.  It  is  an  orange  dye  known  as 
Orange  II  and  is  used  in  dyeing  wool. 


784 


NH2 


(diazotization) 


SO2ONa 

Sulphanilic 
acid 


SO2ONa 

Diazo  compound 


/3-Naphthol 


S02ONa 

Orange  II 
p-Sulpho  benzene  azo-i  Naphthol-2 

(Na  Salt) 

Betol.  Salol.  —  Another  simple  derivative  of  fo/a-naphthol  is  the 
beta-naphthyl  ester  of  salicylic  acid  analogous  to  oil  of  wintergreen, 
the  methyl  ester.  It  is  another  of  the  derivatives  of  this  acid  which 
has  valuable  medicinal  properties.  It  is  known  as  betol,  also  medicin- 
ally as  salol. 

OH 


Betol       or     Salol 
0-Naphthyl  salicylate 

MIXED  SUBSTITUTION  PRODUCTS  OF  NAPHTHALENE 

We  have  mentioned  the  fact  that  most  of  the  dyes  derived  from 
naphthalene  are  mixed  derivatives,  i.e.,  those  in  which  more  than  one 
kind  of  group  is  substituted  in  the  naphthalene  molecule. 


DYES  FROM  NAPHTHALENE  DERIVATIVES  785 

Nitro  Naphthols 

The  simplest  derivatives  of  this  mixed  character  which  yield  dyes 
are  the  nitro  naphthols,  i.e.,  mixed  nitro  and  hydroxyl  substitution 
products.  Recalling  well-known  compounds  of  the  benzene  series  it 
will  be  remembered  that  whereas  mono-nitro  benzene  has  practically 
no  color,  and  di-nitro-benzene  only  a  faint  yellow  color,  the  mixed  tri- 
nitro  phenol  or  picric  acid  has  an  intense  yellow  color  and  was  one  of 
the  first  yellow  dyes  used. 

Martius  Yellow. — In  a  similar  way  the  nitro  naphthalenes  are  only 
faintly  colored  and  are  not  valuable  as  dyes  while  the  mixed  nitro 
and  hydroxy  naphthalenes  are  colored  compounds.  One  of  these  is  a 
yellow  dye  which  was  formerly  used  to  dye  wool  and  silk  but  is  now 
principally  used  in  dyeing  soaps.  It  is  the  2-4-di-nitro  i-naphthol 
which  in  the  form  of  its  sodium,  calcium  or  ammonium  salt  is  known 
as  Martius  yellow. 

ONa 


— NO2 


NO2 

Martius  Yellow 

Naphthol  Yellow  S. — A  sulphonic  acid  derivative  of  this,  viz., 
2-4-di-nitro  i-naphthol  7-sulphonic  acid  in  the  form  of  the  potassium 
salt  is  known  as  Naphthol  Yellow  S. 

OK 


K002S- 


N02 

Naphthol  Yellow  S 

It  is  a  yellow  dye  faster  in  color  than  the  preceding  and  is  used  to  dye 
wool  and  silk. 

50 


786  ORGANIC  CHEMISTRY 

Naphthylamine  Sulphonic  Acids  and  Naphthol  Sulphonic  Acids 

The  amino-sulphonic  acid  derivatives  of  naphthalene  known  as 
naphthylamine  sulphonic  acids  are  interesting  because  of  the  support 
they  give  to  our  ideas  in  regard  to  the  constitution  of  naphthalene  and 
the  possible  isomeric  di-substitution  products.  The  mono-amino 
mono-sulphonic  acid  naphthalene  being  a  di-substitution  product,  is, 
according  to  our  theories,  able  to  exist  in  fourteen  possible  isomeric 
forms  (p.  776).  It  is  a  striking  fact  that  with  this  particular  compound 
all  fourteen  isomers  are  known  thus  giving  strong  support  to  our  ideas 
in  regard  to  the  constitution  of  naphthalene. 

Naphthionic  Acid. — The  most  common  and  most  important  of  these 
fourteen  isomers  is  i -naphthylamine  4-sulphonic  acid.  It  is  known  as 
naphthionic  acid. 

NH2 


SO2OH 

Naphthionic  acid 

This  compound  is  an  important  intermediate  product  in  the 
preparation  of  dyes  as  will  be  explained  presently. 

Eikonogen.  —  A  related  compound,  containing  a  hydroxyl  group 
also,  is  a  common  photographic  developer  known  as  eikonogen.  It 
is  i-amino  2-naphthol  6-sulphonic  acid,  sodium  salt. 

NH2 


NaOO2 

Eikonogen 

Azo  Dyes  from  Naphthalene 

The  most  important  dyes  derived  from  naphthylamine  sulphonic 
acids  and  from  naphthol  sulphonic  acids  result  from  coupling  them  as 
azo  compounds  with  other  rings.  This  coupling  is  effected  through  a 
diazonium  salt  made  by  diazotizing  an  amine  and  bringing  this  di- 


DYES  FROM  NAPHTHALENE  DERIVATIVES 


787 


azonium  salt  in  contact  with  the  naphthalene  compound.  The  amine 
which  supplies  the  additional  rings  may  be  aniline,  C6H5 — NH3, 
benzidine,  H2N— C6H4— C6H4— NH2  (p.  732)  tolidine  H2N— C6H3- 
(CH3)— C6H3(CH3)— NH2  ornaphthylamine  itself.  The  best  examples 
of  this  class  of  azo  dyes  derived  from  naphthalene  which  may  be 
mentioned  at  this  time  are  Congo  Red,  Benzo-purpurin  46,  Naphthol 
Blue  Black  and  Fast  Red  B. 

Congo  Red. — When  benzidine  is  diazotized  a  double  diazo  or  tetrazo 
compound  results  (p.  575)  from  the  diazotization  of  both  of  the  amino 
groups.  This  diazonium  or  tetrazonium  salt  reacts  with  two  molecules 
of  naphthylamine  sulphonic  acid,  naphthionic  acid,  forming  a  double 
azo  or  disazo  compound.  The  sodium  salt  of  this  compound  is  Congo 
red.  The  reactions  are: 


H2N-/  \ 


(diazotization) 


Benzidine 


Cl 


Cl 


NH5 


Di-phenyl  tetrazonium 
chloride 


SO2ONa 

Naphthionic 
acid  (Na  salt) 

NH2 


Cl 


Cl 


Diphenyl  tetrazonium 
chloride 


— N  =  N— 


SO2ONa 

Naphthionic 
acid,  (NojsalQ 


S02ONa 


788 


ORGANIC  CHEMISTRY 


NHs 


_N  =  N— 


SO2ONa 

Congo  Red 

Congo  red  is  a  representative  of  a  group  of  dyes  known  as  substantive 
dyes  which  are  able  to  dye  cotton  without  the  use  of  a  mordant.  It  is 
of  special  interest  historically  as  it  was  the  first  dye  of  this  group  to  be 
made. 

Benzo  purpurin. — Tolidine  is  di-methyl  benzidine,  that  is  it  bears 
the  same  relation  to  toluene  and  ortho-toluidine  that  benzidine  does  to 
benzene  and  aniline.  When  this  is  diazotized  and  the  tetrazonium 
salt  coupled  with  sodium  naphthionate  the  disazo  compound  resulting 
is  a  dye  known  as  benzopurpurin  48,  which  is  also  a  substantive  dye 
of  a  red  color. 


NH 


NH 


— N  = 


SO2ONa 

Benzo-purpurin  46 

Naphthol  Blue  Black. — The  dye  known  as  naphthol  blue  black  is 

an  azo  dye  of  the  same  general  structure  as  the  two  preceding  but 


DYES  FROM  NAPHTHALENE  DERIVATIVES 


789 


its  components  are  more  mixed  in  character.  An  amino  naphthol 
sulphonic  acid,  viz.,  i-amino  8-naphthol  3-6-di-sulphonic  acid,  sodium 
salt,  is  coupled  as  a  disazo  compound  on  one  side  with  a  simple  benzene 
ring  and  on  the  other  with  a  para-nitro  ring.  The  coupling  is  effected 
by  means  of  diazotized  aniline,  benzene  diazonium  chloride,  and  by 
means  of  diazotized  paranitraniline,  p-nitro  benzene  diazonium  chlo- 
ride. The  reactions  being  like  those  already  given  we  need  simply  give 
the  formula  of  the  dye: 


NH 


Naphthol  Blue  Black 

This  dye  is  not  a  substantive  dye.     It  dyes  wool  a  blue  black  color. 

Fast  Red  B,  Bordeaux  B. — One  more  example  of  an  azo  dye  derived 
from  naphthalene  may  be  given  in  which  naphthylamine  is  diazotized 
and  coupled  as  an  azo  compound  with  a  naphthol  sulphonic  acid.  The 
compound  2-naphthol  3-6-di-sulphonic  acid  is  a  dyestuff  intermediate 
known  as  R-salt  (red  salt)  because  it  is  used  in  making  red  dyes. 
When  alpha-naphthylamine  is  diazotized  and  coupled  with  R-salt 
the  resulting  azo  dye  is  known  as  fast  red  B  or  Bordeaux  B.  Its 
constitution  is 


SO2ONa 


Fast  Red  B 

This  dye  also  is  not  a  substantive  dye.     It  dyes  wool  red. 

Illustrations  of  azo  dyes  containing  naphthalene  groups  might  be 
continued  in  very  large  number  but  this  is  undesirable  as  it  would  only 
tend  to  confuse  the  point  to  be  emphasized,  viz.,  that  mixed  amino  or 
hydroxyl  derivatives  of  naphthalene  either  by  diazotization  and  coup- 
ling with  other  compounds,  as  in  the  case  of  fast  red,  or  by  coupling  with 


7QO  ORGANIC  CHEMISTRY 

diazo  compounds  derived  from  other  amines,  such  as  aniline,  benzidine, 
tolidine,  etc.,  as  in  Congo  red,  etc.,  yield  important  azo  dyes.  As  pre- 
viously stated  when  the  azo  dyes  were  first  mentioned  (p.  576),  the  most 
important  dyes  of  this  class  are  those  containing  naphthalene  groups. 
A  very  important  sub-group  of  the  azo  dyes  consists  of  the  substan- 
tive dyes  which  are  able  to  dye  cotton  without  the  use  of  a  mordant. 
This  is  of  great  value  technically.  The  great  variety  of  the  mixed 
naphthalene  derivatives  which  may  become  component  parts  of  such 
dyes  is  very  large  so  that  an  almost  endless  variety  of  products  is  pos- 
sible. In  this  discussion  we  see  emphasized  again  the  very  great  impor- 
tance and  commercial  value  of  the  diazo  reactions. 

Naphthoquinones 

It  will  be  recalled  that  when  para-di-hydroxy  benzene,  hydro- 
quinol,  and  also  other  para  di-substitution  products  of  benzene  are 
oxidized  there  is  obtained  the  compound  known  as  quinone  or  benzo- 
quinone  (p.  636).  In  a  similar  way  para  di-substituted  naphthalenes, 
especially  hydroxyl  and  amino  compounds,  and  in  fact  naphthalene  it- 
self when  oxidized  with  chromic  acid,  yield  a  quinone  analogous  to 
benzoquinone  and  which  is  known  as  alpha -naphthoquinone. 


CH     ^0      nc  CH 

cH       (Cr03)     H( 

C 

c 

H 

O 

a-Naphthoqinone 

A  beta -naphthoquinone  is  also  obtained  by  the  oxidation  of  i -amino  2- 
naphthol  or  other  i-2-di-substituted  naphthalenes.  In  it  the  two  car- 
bonyl  groups  are  formed  with  the  alpha  and  beta  carbons  ortho  to  each 
other  and  it  is  analogous  to  ortho-benzo  quinone.  These  naphthoqui- 
nones  resemble  the  corresponding  benzoquinone  in  their  properties 
and  reactions.  alpha-Naphthoquinone  is  like  benzoquinone  in  that 
it  is  yellow  in  color,  has  a  strong  odor  and  is  volatile  with  steam. 


NAPHTHOQUINONE  AND  NAPHTHALIC  ACID 


791 


beta-Naphthoquinone,  on  the  other  hand,  is  like  0r//f0-benzoquinone 
in  being  odorless  and  non- volatile  with  steam.  It  is  red  in  color.  Both 
yield  oximes  with  hydroxyl  amine  and  the  mono-oximes  are  like  the 
mono-oximes  of  benzoquinone  in  being  pseudo  compounds  with  nitroso 
hydroxyl  compounds  (p.  640).  When  a//>/ja-naphthoquinone  is  treated 
with  hydroxyl  amine  the  same  compound  is  obtained  as  by  the  action 
of  nitrous  acid  on  a^/uz-naphthol.  In  the  same  way  fo/a-naphtho- 
quinone  monoxime  is  pseudo  with  2 -nitroso  i-naphthol. 

O  O 


H2)=N— OH 


(O 

a-Naphthoquinone 


N— OH 


a-Naphthoquinone 
mon-ozime 


OH 


(ON— (OH  + 


H) 


4-Nitroso 
i-naphthol 


a-Naphthol 


Both  of  the  naphthoquinones  yield  0r^0-phthalic  acid  on  oxidation  with 
nitric  acid.  The  constitution  of  the  naphthoquinones  so  far  as  the 
quinone  containing  ring  is  concerned  is  probably  the  same  as  that  of 
benzoquinone  (p.  636). 

Naphthoic  and  Naphthalic  Acids 

By  fusion  of  naphthalene  sulphonic  acids  with  potassium  cyanide  the 
corresponding  cyano  naphthalenes  are  obtained.  These  compounds 
are  nitriles  of  naphthalene  acids.  The  mono-carboxyl  acids  are 
known  as  naphthoic  acids  while  the  di-carboxyl  acids  are  termed 
naphthalic  acids.  The  naphthoic  acids  are  similar  to  benzoic  acid  and 
the  naphthalic  acids  are  like  the  phthalic  acids.  The  naphthalic  acid 


7Q2 


ORGANIC  CHEMISTRY 


with  the  carboxyl  groups  in  the  1-8  or  peri  positions  is  of  especial  inter- 
est because  of  its  similarity  to  or/^-phthalic  acid  in  readily  yielding  an 
anhydride. 


COOH 


/3-Naphthoic  acid 
2-Carboxy  naphthalene 


(OH      H)0 

I  I 

o=c         c=o 


(-H— OH) 


peri-Naphthalic  acid 

i-8-Di-carboxy 

naphthalene 


Naphthalic  anhydride 


ANTHRACENE  AND  DERIVATIVES 
Anthracene 

Together  with  benzene  and  naphthalene  two  other  hydrocarbons 
are  obtained  from  coal  tar  though  in  much  smaller  amounts.  They  are 
anthracene  and  phenanthrene,  both  of  which  have  the  formula  CnHjo. 
Anthracene  together  with  phenanthrene  is  present  in  the  coal  tar  dis- 
tillate which  boils  above  270°.  The  yield  of  anthracene  is  about  0.25 
to  0.45  per  cent  of  the  tar.  The  crude  distillate  is  purified  by  a  second 
distillation  and  separated  into  two  fractions:  (i)  A  product  known 
as  50  per  cent  anthracene  which  is  crystalline  and  still  contains  phenan- 
threne. (2)  A  less  volatile  non-crystalline  oil  known  as  anthracene  oil. 
The  50  per  cent  anthracene  is  largely  used,  just  as  it  is  without  further 
purification,  in  the  preparation  of  alizarin,  its  most  important  derivative. 
To  obtain  pure  anthracene  from  the  crude  50  per  cent  product  it  is 
first  redistilled  after  addition  of  potassium  carbonate  which  forms  a 
non-  volatile  compound  with  a  constituent  known  as  carbazole. 


Carbazole 


NH 


ANTHRACENE  AND  ANTHRAQUINONE  793 

The  distillate  is  then  extracted  with  carbon  di-sulphide  and  sulphuric 
acid  in  which  the  phenanthrene  is  soluble.  The  remaining  anthracene 
is  now  again  distilled,  recrystallized  from  benzene  and  sublimed  by 
means  of  superheated  steam.  Pure  anthracene  crystallizes  in  colorless 
shining  flakes  or  scales,  m.p.  213°,  b.p.  351°.  It  is  soluble  in  benzene 
but  only  slightly  in  alcohol  or  ether.  In  its  chemical  properties  anthra- 
cene resembles  benzene  and  naphthalene.  It  forms  addition  products 
with  hydrogen  or  with  the  halogens  which  are  analogous  to  those  formed 
from  benzene  and  naphthalene.  It  readily  yields  sulphonic  acids  but 
does  not  yield  nitro  derivatives  because  it  is  more  easily  oxidized  by 
nitric  acid  than  is  benzene  or  naphthalene.  When  thus  oxidized  it 
yields  a  quinone  known  as  anthraquinone  analogous  to  benzoquinone 
and  naphthoquinone. 

Condensed  Benzene  Rings.  —  That  anthracene  is  a  condensed 
benzene  ring  compound  is  proven  by  several  syntheses  and  reactions. 

Synthesis  from  Tetra-brom  Ethane.  —  Anschiitz  showed  that  in 
the  presence  of  aluminium  chloride  two  molecules  of  benzene  condense 
with  one  molecule  of  tetra-brom  ethane  and  yield  anthracene.  The 
reaction  may  be  represented  as: 

H 

(R       Br)—  CH—  (Br       H)  ,C 

C6H/       +  |  +       >C6H4       -»     C.H/1  >C6H4 

\tt       Br)—  CH—  (Br       H/  C 

Benzene  Tetra-brom  Benzene  TT 


ethane 

Anthracene 


This  synthesis  indicates  that  in  anthracene  there  are  two 
benzene  rings  linked  together  by  the  tetra-valent  ethane  residue, 

HC—  CH. 

From  ortho-Benzyl  Toluene.—  Such  a  constitution  is  supported  by 
other  syntheses.  When  ortho-benzyl  toluene  is  heated  it  loses  four 
hydrogen  atoms  and  anthracene  is  obtained. 

H 

CH(H)-C6H4(H)  (i)      (_4H) 

r*  TT  /        N/"1  TJ 

C«H4<        >C,H4 


CH(H2)  (2) 

o-Benzyl  toluene  JJ 

Anthracene 


794 


ORGANIC  CHEMISTRY 


From  ortho-Brom  Benzyl  Bromide. — Also  when  ortho-brom  benzyl 
bromide  is  heated  with  sodium,  two  molecules  lose  two  bromine  atoms 
and  two  molecules  of  hydrogen  bromide  and  yield  anthracene. 
H  H 

.(XHBrd)       (i)Br)^  (_2Br) 

CeH4<C  /CeH4          — _^»      CeH4\   |   /CeH4 

N/-I-* 


(2) 

o-Brom  benzyl  bromide 


(2)BrH)CX  (~2HBr) 

H  H 

Anthracene 

From  Phenyl  ortho-Tolyl  Ketone. — When  phenyl  ortho-tolyl 
ketone,  C6H5— CO— C6H4— CH3,  is  heated  with  zinc  dust  water  is 
lost  and  anthracene  results. 

H 


/ 

6H/ 


(~H20) 

H^-^/"*    TT  . f~*    TT 

xL,6Al4  Cerl 


H 


H 

Phenyl  o-tolyl  ketone  Anthracene 

Thus  anthracene  must  be  constituted  of  two  benzene  rings  each  one 
linked  by  two  ortho  positions  to  an  intervening  ethane  residue.  If  such 
a  formula  is  constructed  of  tetra-hedral  carbons,  which  will  be  clear 
if  models  are  used,  we  shall  have  the  following: 

H 
C 


H 


C6H4 


6H4 


or 


H 


or 


ANTHRACENE  AND  ANTHRAQUINONE  795 

Three  Benzene  Nuclei.  —  Just  as  naphthalene  contains  two  benzene 
nuclei  it  will  be  seen  that  anthracene  similarly  contains  three  benzene 
nuclei.  In  other  words  they  are  condensed  benzene  ring  compounds, 
the  former  of  two  and  the  latter  of  three  rings.  In  naphthalene  we  have 
shown  that  either  of  the  two  nuclei  may  remain  as  a  benzene  ring  on 
the  destruction  of  the  other.  In  the  case  of  anthracene  we  can  show  with 
equal  proof,  as  has  already  been  done  in  the  syntheses  just  given,  that 
the  two  outside  nuclei  are  true  benzene  rings.  It  has  never  been 
possible,  however,  either  to  start  with  a  benzene  ring  as  the  center  and 
build  up  anthracene  by  adding  on  the  two  outside  nuclei  or  to  decompose 
the  compound  in  such  a  way  that  the  center  nucleus  remains  as  a  ben- 
zene ring.  Nevertheless  the  evidence  is  clear  that  in  reality  there  are 
three  benzene  nuclei  in  the  compound,  the  center  nucleus  being  less 
strongly  aromatic  in  character  due  to  its  condition.  Facts  bearing  on 
this  question  are  to  be  found  in  the  study  of  some  of  the  derivatives  of 
anthracene  and  these  will  now  be  considered. 

Anthraquinone 

When  anthracene  is  treated  with  nitric  acid  instead  of  yielding  nitro 
substitution  products  as  do  benzene  and  naphthalene  it  becomes  oxi- 
dized to  a  compound  known  as  anthraquinone,  the  composition  of  which 
is  Ci4H8O2  and  which  may  be  reduced  back  to  anthracene  by  heating 
with  zinc  dust.  The  relationship  in  composition  between  anthracene 
and  anthraquinone  is  the  same  as  between  benzene  and  benzoquinone 
and  between  naphthalene  and  naphthoquinone. 

C6H6  C6H402 

Benzene  Benzoquinone 


CioH8 

Npahthalene  Naphthoquinone 

C14Hift  C14H802 

Anthracene  Anthraquinone 

This  would  indicate  a  similarity  in  constitution  in  these  three  quinones 
and  this  is  supported  by  the  following  synthesis  which  also  agrees 
with  the  constitution  of  anthracene  as  already  given. 

Synthesis  from  Phthalic  Acid.—  ortho-Phthattc  acid  yields  a  mono- 
brom  derivative  in  which  the  bromine  is  ortho  to  one  carboxyl  and 
meta  to  the  other,  i.e.,  i-2-dicarboxy  3-brom  benzene.  This  being 
an  or/fo-phthalic  acid  yields  an  anhydride.  This  anhydride  condenses 


796 


OPGANIC  CHEMISTRY 


with  benzene  in  the  presence  of  aluminium  chloride  and  the  product 
is  2-benzoyl  3-brom  benzole  acid. 


— COOH 
— COOH 

o-Phthalic  acid 


Br 


—COOH 


—COOH 


(-H20) 


i-2-Di-carboxy 
3-brom  benzene 


(AlCla) 


2-Benzoyl  3-brom 
benzole  acid 


When  this  2-benzoyl  3-brom  benzole  acid  is  heated  with  sulphuric  acid 
water  is  lost  and  brom  anthraqulnone  is  obtained. 


(-H— OH) 


2-Benzoyl  3-brom  benzoic||acid 


Br 

Brom  anthraquinone 


This  synthesis  is  of  the  same  general  character  as  that  of  anthracene 
from  phenyl  orlho-tolyl  ketone  (p.  794).  In  effect  it  is  the  condensation, 
by  the  elimination  of  water,  of  phthalic  anhydride  and  benzene  with  the 
formation  of  anthraquinone  which  we  may  represent  as 


ANTHRACENE  AND  ANTHRAQUINONE 


Anthraquinone 


Anthraquinone  must  therefore  have  the  constitution  of  two  benzene 
rings  linked  together  by  two  carbonyl  groups.  These  two  carbonyl 
groups  are  ortho  to  each  other  in  the  ring  which  was  originally  ortho- 
phthalic  acid.  That  these  carbonyl  groups  become  linked  to  the  second 
benzene  ring  in  the  ortho  positions  also  is  proven  by  the  conversion  of 
brom  anthraquinone  into  0r//f<?-phthalic  acid.  By  means  of  potassium 
hydroxide  the  brom  anthraquinone  is  converted  into  hydroxy  anthra- 
quinone and  this  by  oxidation  yields  ortho -phthalic  acid. 


+K— OH 


Br 

Brom  anthraquinone 


+0 


'Y^\ 

11 

HOOC— k          J 


o-Phthalic 


OH 

Hydroxy  anthraquinone 

In  the  preceding  reactions  the  benzene  nucleii  have  been  numbered 
I  and  II  in  order  to  follow  their  course  through  the  various  transforma- 
tions. It  may  be  readily  seen,  therefore,  that  the  benzene  nucleus  in 
brom  anthraquinone  which  remains  as  a  benzene  ring  in  0r//?0-phthalic 
acid  is  the  nucleus  which  does  not  contain  bromine.  This  was  derived 
from  the  benzene  constituent  of  the  synthesis  and,  in  anthraquinone, 
it  is  linked  to  the  carbonyl  groups  by  ortho  positions.  Therefore,  both 
benzene  nucleii  in  anthraquinone  are  linked  by  ortho  positions  and  both 
are  derived  from  true  benzene  ring  compounds  or  may  remain  as  ben- 
zene rings  on  the  decomposition  of  the  quinone. 


7Q8 


ORGANIC  CHEMISTRY 


The  constitutions  of  anthracene  and  anthraquinone  are  thus  es- 
tablished as  reciprocal  oxidation  and  reduction  products.  The  com- 
plete structural  formulas  may  be  represented  as  follows: 


0(HN03) 


CH     +  H(Zn  +  heat) 


HC 


Anthracene 


HC 


CH 


CH 


O 

Anthraquinone 

Character  of  Center  Nucleus. — As  was  stated  in  connection  with 
anthracene  itself  we  can  not  say  positively  as  to  the  character  of  the 
center  nucleus  in  either  the  hydrocarbon  or  the  quinone.  In  anthra- 
cene the  aliphatic  character  of  this  center  nucleus  is  indicated  by  its 
formation  from  an  ethane  residue,  by  the  tetra-brom  ethane  synthesis. 
This  does  not,  however,  preclude  the  possibility  of  its  becoming  a  true 
benzene  nucleus  when  condensed  with  two  benzene  rings,  for  benzene 
itself  may  be  made  from  aliphatic  hydrocarbons,  from  acetylene  by 
polymerization  (p.  478),  and  from  hexane  through  hexa-methylene 
with  the  loss  of  hydrogen  after  the  formation  of  the  cyclo-paraffin 
(p.  469).  Also  naphthalene,  in  which  there  is  no  doubt  of  the  benzene 
character  of  the  two  nuclei,  may  have  one  nucleus  formed  from  an 
aliphatic  chain  as  in  the  syntheses  given  (p.  767)  from  phenyl  butylene 
bromide,  from  phenyl  vinyl  acetic  acid  and  from  tetra-carboxy  ethane. 
In  the  same  way  the  facts  in  regard  to  anthraquinone  do  not  prove 


ANTHRACENE   AND   ANTHRAQUINONE  799 

that  the  center  nucleus  is  not  of  benzene  character.  Anthraquinone 
lacks  distinctive  quinone  character.  It  is  not  colored,  has  no  strong 
odor  and  is  not  volatile  with  steam.  On  the  other  hand,  it  resembles 
ketones  being  like  benzophenone,  di-phenyl  ketone.  In  fact  its 
structure  is  clearly  that  of  a  di-phenyl  di-ketone.  The  progressive 
loss  of  quinone  character  from  benzoquinone,  to  naphthoquinone, 
to  anthraquinone,  and  the  relation  of  these  quinones  to  their  corre- 
sponding hydrocarbons,  is  very  interesting  and  instructive.  The 
single  benzene  ring  of  benzene  itself  can  not  be  directly  oxidized  to  the 
quinone  and  the  quinone  when  obtained  has  very  distinctive  char- 
acters. These  characters  are  distinct  from  those  of  ketones  though 
the  structure  of  benzoquinone  is  probably  that  of  a  di-ketone  (p.  636). 
Naphthalene*  on  the  other  hand,  consisting  of  two  benzene  nuclei  is 
able  to  be  oxidized  directly  to  naphthoquinone  by  means  of  chromic 
acid.  Here  the  benzene  nucleus  which  yields  the  quinone  group  is 
not  in  itself  a  complete  benzene  ring  as  it.  possesses  only  four  out  of 
six  carbons  independent  of  the  other  nucleus.  It  must,  therefore,  be 
less  strongly  benzene  in  its  character,  yet  it  may  become  a  complete 
ring  on  the  destruction  of  the  other  nucleus.  The  character  of  naph- 
thoquinone is  also  less  strongly  quinone-like  and  more  like  a  ketone. 
Now  in  anthracene  the  center  nucleus  which  yields  the  quinone  group 
is  still  less  a  complete  benzene  ring  in  itself,  as  it  possesses  only  two 
carbons  independent  of  the  other  two  nuclei.  It  is  thus  even  less 
strongly  benzene  in  character  than  either  nucleus  in  naphthalene  and 
in  fact  has  never  been  retained  as  a  complete  ring  by  the  destruction 
of  the  other  two  nuclei.  Anthracene,  therefore,  is  able  to  have  this 
center  nucleus  oxidized  to  the  quinone  group  more  easily  than  in  the 
case  of  naphthalene,  for  anthraquinone  is  obtained  by  simply  oxidizing 
the  hydrocarbon  with  nitric  acid.  Also,  the  quinone  character  of 
anthraquinone  is  still  less  than  of  naphthoquinone  and  it  is  much  more 
like  a  ketone. 

That  the  center  nucleus  in  anthracene  and  anthraquinone  is  in 
reality  a  true  benzene  nucleus  is  supported  simply  by  the  structural 
and  space  relations  of  the  constituent  carbon  atoms  which  according 
to  the  tetra-hedral  theory  are  exactly  the  same  as  in  benzene,  in  the 
two  nuclei  of  naphthalene,  or  the  other  two  nuclei  of  anthracene  it- 
self. For  all  of  these  nuclei  the  true  benzene  character  is  fully  proven. 
Thus  while  it  is  best  not  to  place  too  much  emphasis  upon  the  three 


800  ORGANIC  CHEMISTRY 

benzene  nuclei!  structure  of  anthracene  and  anthraquinone  there  seems 
to  be  no  real  reason  for  not  accepting  it,  as  it  is  not  contrary  to  the 
evidence  derived  from  either  the  syntheses  of  the  compounds  or  their 
properties  and  it  is  in  accord  with  the  tetra-hedral  theory  of  carbon 
and  its  application  to  the  benzene  ring. 

Isomerism. — An  examination  of  the  formula  for  anthracene  will 
show  that  the  number  of  isomeric  substitution  products  may  be  greater 
in  number  than  in  the  case  of  naphthalene.  The  facts  in  regard  to 
the  mono-  and  di-substitution  products  are  that  there  are  three  mono- 
substitution  products  and  fifteen  di-substitution  products  with  like  substit- 
uents.  Numbering  the  positions  in  the  anthracene  formula  we  have: 


The  mono-substitution  product  with  the  substituent  in  positions 
i,  4,  5  or  8,  is  named  alpha;  in  positions  2,  3,  6  or  7,  beta;  and 
in  position  9  or  10,  gamma.  If  two  substituents  are  alike  the 
following  fifteen  isomeric  di-substitution  products  are  possible:  1-2, 
1-3,  1-4,  1-5,  1-6,  1-7,  1-8,  1-9,  i-io,  2-3,  2-6,  2-7,  2-9,  2-10,  9-10. 
Of  the  derivatives  of  anthracene  a  large  number  are  known  but  only 
two  will  be  taken  up  in  detail,  viz.,  anthraquinone,  which  we  have 
already  considered,  and  alizarin. 

Alizarin 

Turkey  Red. — Alizarin  is  the  chief  constituent  of  the  coloring  mat- 
ter Turkey  red,  which  has  been  known  since  ancient  times  and  which 
was  obtained  from  the  root  of  the  madder  plant,  Rubia  tinctorum  L. 
The  substance  is  of  special  interest  because  the  determination  of  its 
constitution  was  one  of  the  early  triumphs  of  organic  chemistry  and 
because  it  was  the  first  natural  dye  to  be  synthetically  prepared.  The 
name  is  derived  from  the  oriental  name  for  the  madder,  viz.,  alizari. 
In  the  madder  root  it  is  present  as  a  glucoside  known  as  ruberythric 
acid,  which,  on  hydrolysis  by  fermentation  or  by  boiling  with  acids, 
yields  glucose  and  alizarin.  Alizarin  is  a  solid  which  sublimes  as  orange 
red  needles,  m.p.  289°,  insoluble  in  water  but  slightly  soluble  in  alcohol. 


ALIZARIN  801 

Synthesis,  Graebe  and  Liebermann.  —  The  determination  the  of 
constitution  of  alizarin  and  its  synthetic  preparation  are  both  due 
largely  to  the  work  of  Graebe  and  Liebermann  in  1868. 

Reduction  to  Anthracene.  —  They  first  obtained  the  hydrocarbon 
mother  substance  which  they  proved  to  be  anthracene,  and  which  was 
obtained  on  reducing  alizarin  by  dry  distillation  with  zinc  dust.  This 
method  of  reduction  was  discovered  by  Baeyer  and  has  been  referred 
to  before  as  being  applicable  to  the  conversion  of  anthraquinone  into 
anthracene  (p.  795).  The  action  is  due  to  the  presence  of  zinc  oxide 
in  the  zinc  dust.  Alizarin  has  the  composition  Ci4H8O4.  Therefore 
the  empirical  reaction  is 

+  5H2(Zn  +  ZnO) 
C14H804  —  C14H10  +  4H20 

Alizarin  Anthracene 

The  relationship  in  composition  between  anthracene,  anthraquinone 
and  alizarin,  viz., 


Ci4Hio 

Anthracene  Anthraquinone  Alizarin 

led  them  to  believe  that  anthraquinone  was  an  intermediate  product 
and  that  alizarin  might  be  di-hydroxy  anthraquinone. 

i-2-Di-hydroxy  Anthraquinone,  Baeyer  and  Caro.  —  To  test  this 
point  they  prepared  a  di-brom  anthraquinone  and  fused  it  with  potas- 
sium hydroxide.  The  product  proved  to  be  alizarin,  thus  establishing 
it  as  di-hydroxy  anthraquinone. 

+  Br  +  K—  OH 

Ci4H802          —      Ci4H6Br2O2          —       Ci4H6(OH)2O2  or  C14H8O4 

Anthraquinone  Di-brom  anthra-  Di-hydroxy  anthraquinone 

quinone  Alizarin 

The  remarkable  thing  is,  that  while  there  are  ten  possible  di-brom  or 
di-hydroxy  anthraquinones,  the  particular  one  necessary  was  obtained 
by  Graebe  and  Liebermann.  The  positions  of  the  two  hydroxyl  groups 
were  determined  by  Baeyer  and  Caro.  When  alizarin  is  heated  pyro- 
catechinol,  1-2  -di-hydroxy  benzene,  is  obtained.  Also  when  pyro- 
catechinol  is  heated  with  orf/w-phthalic  acid  and  sulphuric  acid  alizarin 
results.  This  last  synthesis  is  analogous  to  that  of  anthraquinone  from 
benzene  and  0f//w-phthalic  acid  (p.  796). 


51 


802 


J-co/ 

Pathafic  anhydride 


ORGANIC  CHEMISTRY 

OH 


-COV  H) 

(0  + 


— OH 


Pyro-catechinol 


OH 


OH 


O 

Alizarin 

This  relationship  of  alizarin  to  pyro-catechinol  proves  that  the  two  hy- 
droxyl  groups  must  be  ortho  to  each  other,  but  this  condition  is  possible 
if  the  hydroxyls  are  either  1-2  or  2-3.  Baeyer  and  Caro  established 
the  positions  as  1-2  as  follows.  When  phenol  is  heated  with  ortho- 
phthalic  acid  and  sulphuric  acid  two  mono-hydroxy  anthraquinones  are 
obtained. 

OH 


— H20). 


—OH 


O 

i-Hydroxy 
anthraquinone 


O 

2-Hydroxy 
anthraquinone 


ALIZARIN  803 

As  will  be  seen,  only  these  two  mono-hydroxy  compounds  are  possible. 
Now  both  of  these  mono-hydroxy  anthraquinones  yield  alizarin  by  the 
introduction  of  a  second  hydroxyl  group.  The  only  constitution  pos- 
sible for  a  di-hydroxy  anthraquinone  obtained  from  both  of  these  two 
mono-hydroxy  anthraquinones  is  the  i-2-di-hydroxy  compound.  As 
alizarin  is  thus  obtained  the  two  hydroxyl  groups  in  it  must  be  in  the 
1-2  positions  and  not  in  the  2-3  positions. 


O 


OH 


O 

i-Hydroxy  anthraquinone 


OH 


—OH 


i -2 -Di-hydroxy  anthraquinone 
Alizarin 


O 


OH 


O 

2-Hydroxy  anthraquinone 

Commercial  Synthesis. — In  their  work  Graebe  and  Liebermann 
used  a  second  synthesis  for  preparing  alizarin.  When  anthraquinone 
mono-sulphonic  acid  is  fused  with  potassium  or  sodium  hydroxide 
alizarin  is  obtained.  In  this  synthesis  the  alkali  fusion  replaces  the 
sulphonic  acid  group  with  hydroxyl  and  at  the  same  time  oxidizes  the 


804 


ORGANIC  CHEMISTRY 


neighboring  hydrogen  to  hydroxyl.  A  modification  of  this  synthesis 
is  the  commercial  process  for  making  alizarin  today.  Crude  anthra- 
cene, known  as  50  per  cent  anthracene  (p.  792),  is  converted  into  crude 
anthraquinone  by  oxidation  with  sodium  bichromate,  Na2Cr2O7,  and 
sulphuric  acid.  The  crude  anthraquinone  is  then  heated  with  ordinary 
sulphuric  acid  to  100°.  This  treatment  sulphonates  the  impurities 
present  and  allows  their  removal  from  the  non-sulphonated  anthra- 
quinone. The  thus  purified  anthraquinone  is  then  sulphonated  by 
heating  to  160°  with  50  per  cent  fuming  sulphuric  acid.  The  product 
is  largely  anthraquinone  i-sulphonic  acid.  Instead  of  fusing  this  with 
alkali  alone  the  sodium  salt  of  the  sulphonic  acid  is  treated  with  a  mix- 
ture of  sodium  hydroxide  and  potassium  chlorate  and  heated  in  an  auto- 
clave to  1 80°  for  48  hours.  The  potassium  chlorate  is  a  more  active 
oxidizer  than  the  alkali  alone,  the  product  of  the  combined  alkali 
fusion  and  oxidation  being,  as  in  Graebe  and  Liebermann's  original 
synthesis,  alizarin.  The  reactions  are: 


Anthraquinone 
i -Sulphonic  acid 


8oS 


(KC103) 


O 

i-Hydroxy 
anthraquinone 


OH 


—OH 


In  this  synthesis  it  is  interesting  that  it  is  the  mono-sulphonic  acid  of 
anthraquinone  and  not  the  di-sulphonic  acid  which  is  the  intermediate 
product.  Other  syntheses  have  been  used  commercially.  Anthraqui- 
none may  be  converted  into  alizarin  without  sulphonation  by  treating 
it  with  a  mixture  of  sodium  hydroxide,  potassium  hydroxide  and  so- 
dium chlorate  and  heating  to  200°.  Also  electrolytically  by  passing  a 
current  through  a  mixture  of  anthraquinone  and  fused  potassium 
hydroxide. 

Industrial  Importance. — The  synthesis  of  alizarin  by  Graebe  and 
Liebermann  was  the  first  case  of  a  common  natural  dye  being  prepared 
in  the  laboratory.  As  the  synthesis  starts  with  anthracene,  a  substance 
obtained  in  good  yields  from  coal  tar,  it  affords  at  once  a  cheap  commer- 
cial source  for  the  synthetic  preparation  of  a  natural  product.  Hardly 
any  synthesis  that  has  been  worked  out  in  the  laboratory  has  had  such 
an  immediate  effect  upon  industry  as  this  one,  and  in  addition  to  this  it 
exerted  a  strong  influence  upon  similar  syntheses  of  other  dyes.  In 
1868  Turkey  red  was  a  very  common  and  valuable  dye  and  the  growth 
of  the  madder  plant,  in  France  especially,  was  an  important  industry. 
Iii  their  original  paper  Graebe  and  Liebermann  make  this  statement: 


806  ORGANIC  CHEMISTRY 

"We  need  not  indicate  the  importance  of  our  discovery  to  the  madder 
industry  if  it  is  possible  to  make  it  a  technical  success."  That  their 
synthesis  was  a  success  may  be  seen  from  a  few  facts.  In  1868  France 
produced  about  250,000  tons  of  madder,  exporting  over  $5,000,000 
worth  of  products.  In  three  years  the  exportation  fell  to  about 
$800,000  and  before  a  decade  had  passed  the  growth  of  madder  had 
practically  ceased.  A  common  saying  in  the  madder  country,  as  given 
by  Schorlemmer  is:  "it  is  no  longer  grown  as  it  is  now  made  by  ma- 
chinery." When  we  consider  later  the  synthetic  preparation  of  indigo 
we  shall  find  that  a  similar  result  was  effected. 

The  use  of  alizarin  as  a  dye  depends  upon  the  fact  that  with  mor-x 
dants  of  metallic  oxides  it  forms  insoluble  lakes  which  are  deposited  on 
the  fibers  of  the  cloth  and  thus  dye  it.  These  lakes  are  of  different 
colors  depending  upon  the  metallic  salt  used.  Aluminium  gives  a  red 
color  known  as  Turkey  red.  Ferrous  iron  gives  black-violet  and  ferric 
iron  a  brown-black.  Tin  produces  a  red-violet  color  as  stannous  salts 
and  a  violet  as  stannic.  Chromium  salts  give  a  brown-violet  color. 

Nitro,  amino  and  sulphonic  acid  derivatives  of  alizarin  are  also  dyes 
of  various  colors  and  are  known  as  alizarin  orange,  alizarin  maroon, 
alizarin  red,  etc.  Also  there  is  present  in  the  madder  root  another  dye 
compound  known  as  purpurin  which  is  i-2-4-tri-hydroxy  anthraqui- 
none.  Isomeric  tri-hydroxy  anthraquinones  are  dyes  also  but  it  is 
interesting  that  in  all  of  these  poly-hydroxy  anthraquinones  which  are 
dyes  two  of  the  hydroxyls  are  always  in  the  1-2  positions. 

PHENANTHRENE  AND  DERIVATIVES 
Phenanthrene 

The  third  hydrocarbon  consisting  of  condensed  benzene  nuclei 
similar  to  naphthalene  and  anthracene  is  known  as  phenanthrene.  It 
has  the  composition  CnHio  and  is  thus  isomeric  with  anthracene.  It 
is  found  associated  with  the  latter  in  the  coal  tar  distillate  boiling  above 
270°  and  is  separated  by  solution  in  carbon  disulphide  (p.  793).  It  is 
a  solid  crystallizing  in  colorless  flakes,  m.p.  99°,  b.p.  340°.  It  is  only 
slightly  soluble  in  water,  a  little  more  soluble  in  alcohol  and  soluble  in 
ether. 

Synthesis  from  Stilbene  and  Di-tolyl. — Two  similar  syntheses 
indicate  the  constitution  of  phenanthrene.  When  stilbene,  (p  .  762), 


PHENANTHRENE  AND  DERIVATIVES 


807 


C6H5—  CH  =  CH—  C6H5  is  heated  it  loses  two  hydrogens  andphenan- 
threne  results.  Also  ortho-di-tolyl,  CH3-C6H4-C6H4-CH3,  when 
heated  loses  four  hydrogens  and  yields  phenanthrene.  These  re- 
actions yielding  the  same  product  must  necessarily  be  represented  as 
follows: 

:  CeH5 


C6H5-CH 

stilbene 

C6H4-CH3 


C6H4—  CH 

o-Di-tolyl 


C6H4-CH 

Phenanthrene 

G6H4-CH 


C6H4—  CH 

Phenanthrene 


Expressing  a  compound  of  this  constitution  by  means  of  benzene  rings 
we  have: 


CH 


or 


CH 


Phenanthrene 


Such  a  formula* represents  a  compound  consisting  of  three  condensed 
benzene  nuclei.  More  conclusive  proof  of  the  constitution  is  afforded 
by  other  syntheses  and  by  the  decomposition  of  the  hydrocarbon. 
From  ortho-Amino  alpha-Phenyl  Cinnamic  Acid. — Referring  to 
cinnamic  acid  (p.  697)  the  constitution  of  ortho-amino  alpha -phenyl 
cinnamic  acid  will  be  as  shown  by  the  following  relationships. 


8o8 


ORGANIC  CHEMISTRY 


C6H5— C— H 


C6H5— C— H 


H— C— COOH    C6H5— C— COOH 

Cinnamic  acid  o-Phenyl  cinnamic  acid 


(2)  (I) 

NH2— C6H4— C— H 


C6H5— C— COOH 

o-Amino    a-phenyl 
cinnamic  acid 


When  this  amino  derivative  is  diazotized  and  decomposed  in  the  pres- 
ence of  metallic  copper  (Sandmeyer  reaction)  the  two  benzene  rings 
become  linked  together  yielding  a  mono-carboxy  acid  of  phenanthrene 
and  this  by  loss  of  carbon  dioxide  yields  phenanthrene. 


HC 


C— COOH 


(diazotization  and 
decomposition  with  Cu) 


o-Amino  a-phenyl 
cinnamic  acid 


phenanthrene 


Phenanthrene 


PHENANTHRENE  AND  DERIVATIVES 


809 


From  ortho-Brom  Benzyl  Bromide.-From  this  constitution  for 
Phenanthrene  and  its  similarity  to  the  constitution  of  anthracene  both 
bemg  made  up  of  three  benzene  nucleii,  it  will  not  be  surprising  Sat 


benzyl  bromide  (p.  794),  which  by  ^  loof 
molecules  of  hydrobromic  acid  and  two  atoms  of  bromine,  by  heating 
with  alkali,  yields  both  compounds. 


H 

C(HBr)    (Br) 


(BrH)C 

o-Brom  benzyl  bromide          TT  (  — 2HBr) 

(2  mo/.)  -H.  v     >    ' 

(-2Br) 


-2HBr) 


CH 


Phenanthrene 


o-Brom  Benzyl  bromide 

(2  mol.) 


The  different  manner  in  which  the  loss  of  bromine  and  hydrogen  occurs 
is  plainly  shown  and  the  two  hydrocarbons  being  isomeric  compounds 
the  difference  in  constitution  is  apparent. 

Phenanthraquinone,  Di-phenic  Acid.— Two  derivatives  of  phenan- 
threne may  be  simply  mentioned.  On  oxidation  with  chromic  acid 
phenanthrene  yields  a  quinone  known  as  phenanthraquinone.  By 
further  oxidation  the  intermediate  benzene  nucleus  breaks  and  a 
di-carboxy  acid  known  as  di-phenic  acid  is  obtained  (p.  733). 


8io 


ORGANIC  CHEMISTRY 


0 


-COOH 


COOH 


Phenanthraquinone  Di-phenic  acid 

Retene,  Pyrene. — Other  condensed  benzene  nuclei  compounds  are 
known.  Pyrene  is  a  four  benzene  nuclei  compound  and  retene  ia  a 
condensed  ring  compound  found  in  pine  tar. 


4.  HYDROGENATED  BENZENE  COMPOUNDS 

One  more  class  of  hydrocarbons  is  yet  to  be  considered  which 
includes  compounds  more  closely  related  to  benzene  and  its  homo- 
logues  than  to  any  of  the  poly-ring  or  condensed  ring  hydrocarbons 
such  as  di-phenyl.  naphthalene  or  anthracene.  The  hydrocarbons  to 
be  studied  now  are  of  two  groups  known  as  naphthenes  and  terpenes. 
From  the  terpenes  a  very  important  series  of  derivatives  is  obtained 
which  includes  the  common  substance  known  as  camphor.  Also  we 
shall  consider  the  group  of  substances  known  as  essential  oils,  such  as 
oils  of  turpentine,  dove,  lemon,  geranium,  etc.,  many  of  which  are 
terpenes.  Finally  the  interesting  and  valuable  product  rubber  or 
caoutchouc  is  also  a  terpene. 

NAPHTHENES 

The  petroleum  oil  which  is  found  in  the  Caucasus  in  the  region  of 
the  Black  Sea  and  commonly  known  as  Russian  petroleum  differs  from 
American  petroleum  in  that  while  the  latter  contains  almost  entirely 
hydrocarbons  of  the  aliphatic  series,  the  former  contains  hydrocarbons 
known  as  naphthenes  which  are  hydrogenated  benzene  compounds. 

Hydro  Benzenes. — In  discussing  the  constitution  of  benzene  (p. 
468)  it  was  shown  that  by  the  addition  of  six  hydrogen  atoms  to  the 
benzene  molecule  it  was  converted  into  cyclo-hexane  or  hexa-hydro 
benzene.  The  addition  of  hydrogen  according  to  the  above  reaction 
takes  place  when  benzene  and  hydrogen  are  passed  over  finely 
divided  nickel,  Sabatier  and  Senderens  reaction.  Intermediate  be- 
tween benzene  and  hexa-hydro  benzene  we  have  partially  hydro- 
genated products  resulting  from  the  addition  of  two  or  four  hydrogen 
atoms  per  molecule  of  benzene.  These  hydro-benzenes  are  the 
naphthenes.  They  are  also  known  as  hydro-aromatic  compounds. 

The  series  is  as  follows: 

8n 


8l2 


ORGANIC  CHEMISTRY 


H2 


^ 
HCj^  ^ 

HCI.J 


CH 


CH 


H2 

Di-hydro  benzene 


CH2 


H2C 


H2 

Tetra-hydro  benzene 


These  naphthene  hydrocarbons  are  the  mother  substances  of  important 
derivatives  some  of  which  have  already  been  considered  as  direct 
derivatives  of  benzene  but  which  may  also  be  regarded  as  derivatives  of 
the  naphthenes. 

Quinone  and  Phloroglucinol.  —  Benzoquinone  or  quinone  (p.  636) 
is  considered  a  di-ketone  derivative  of  benzene  because  of  its  relation  to 
hydroquinol  or  para-di-hydroxy  benzene.  It  may  also  be  considered 
as  an  oxygen  derivative  of  di-hydro  benzene. 


OH 

Hydroquinol 


Hc 


Di-hydro  benzene 


NAPHTHENES 


813 


Also  phloroglucinol  the  i-3-5-tri-hydroxy  benzene  may  have  the 
tautomeric  constitution  of  a  tri-ketone  (p.  621)  in  which  case  it  is  a 
tri-oxy  derivative  of  hexa-hydro  benenze. 

OH  O 


HO— C 


or 


Ptloroglucinol 


i  -3  -5  -Tri  -hy droxy 
benzene 


o=c 


c=o 


i-3-5-Tri-oxy 

hexa-hydro 

benzene 


H2C 


CH2 


H2 

Hexa-hydro  benzene 


CYCLO  HEXANOLS 


A  less  complete  oxidation  of  hexa-hydro  benzene  than  that  repre- 
sented by  the  relationship  of  the  tri-ketone  compound  above  yields  a 
series  of  cyclic  secondary  alcohols  some  of  which  are  natural  substances. 
Their  relationship  to  hexa-hydro  benzene  is  as  follows: 
H2 
C 


CHOH 


CHOH 


H2C 


H 


C 
H2 

Cyclo-hexane 

Hexahydro 

benzene 


CHOH 

Cyclo  hexan- 

di-ol 
Chinitol 


814  ORGANIC  CHEMISTRY 

CHOH  CHOH 

HOHCr^ 


HOHcL        JCHOH   HOHcL    ^I 


C  CHOH 

HCyclo  hexan- 
2  hex-ol 

Cyclo  hexan-  Inositol 

pent-ol 
Quercitol 

Chinitol,  Quercitol,  Inositol 

The  last  three  compounds,  the  two,  five  and  six  hydroxyl 
derivatives  of  hexa-hydro  benzene,  are  natural  substances  known  as 
chinitol,  qurecitol  or  acorn  sugar  found  in  acorns,  and  inositol  or  muscle 
sugar  found  in  animal  muscle  tissue.  These  compounds  are  all  sweet 
in  taste  and  were  at  one  time  supposed  to  be  true  sugars.  This  was 
indicated  also  by  the  fact  that  the  last  is  isomeric  with  glucose,  its 
composition  being  CeH^Oe.  However,  the  compound  is  not  fermented 
by  'yeast  zymase,  it  does  not  reduce  Fehling's  solution  and  does  not 
react  with  phenyl  hydrazine.  It  is  therefore  not  a  true  sugar.  Its 
relation  to  benzene  is  shown  also  by  the  fact  that  on  reduction  with 
hydriodic  acid  it  yields  phenol  and  benzene.  Inositol  is  known  as 
muscle  sugar  because  of  its  sweet  taste  and  because  it  is  found  in 
animal  muscle  tissue,  especially  in  the  heart  and  brain.  It  is  also 
found  in  various  leaves,  roots  and  seeds,  such  as  peas,  beans  and  cereals. 

Phytin.  —  In  the  latter  it  is  present  in  combination  as  a  substance 
known  as  phytin.  This  substance  is  a  calcium  or  magnesium  salt  of 
a  hexa-  phosphoric  acid  ester  of  inositol.  It  is  the  compound  in  which 
most  of  the  phosphorus  present  in  seeds  is  contained. 

TERPENES 

Strictly  speaking  the  terpenes  are  hydrocarbons  which  are  present 
in,  or  are  obtained  by  steam  distillation  from,  certain  natural  products, 
such  as  camphor  and  oil  of  turpentine;  certain  of  the  so-called  essential 
or  ethereal  oils,  mostly  from  conifer  or  citrus  plants,  e.g.,  oil  of  lemon; 
various  plant  resins,  and  India  rubber  or  caoutchouc.  They  are  the 
mother  substances  of  the  individual  constituents  of  the  products  just 
mentioned.  In  general  usage  the  name  terpenes  includes  not  only  the 
hydrocarbons  but  the  various  derivatives  referred  to  above. 


TEKPENES 

HYDROCARBONS 

Terpenes  and  Hemi-terpenes.— The  more  common  terpene  hydro- 
carbons or  terpenes  in  the  narrow  sense,  such  as  those  obtained  from 
oil  of  turpentine  and  lemon  oil,  have  the  composition  represented  by  the 
formula  CioH16.  This  is  considered  as  the  terpene  unit  and  certain 
members  of  the  series  which  have  the  composition  C5H8  are  termed 
hemi-ter  penes. 

Olefine  and  Cyclic  Terpenes. — Two  distinct  groups  are  known 
which  have  entirely  different  structure.  The  first  and  smaller  group 
includes  strictly  aliphatic  hydrocarbons  belonging  to  the  olefine  or 
ethylene  unsaturated  series.  The  second  group,  which  is  much  larger, 
includes  cy do-aliphatic  hydrocarbons  or  as  we  have  previously  described 
them  the  hydro-aromatic  hydrocarbons.  Thus  we  have: 
I.  Olefine  terpenes,  open  chain  compounds. 

II.  Cyclic  terpenes,  hydro-aromatic  compounds. 

I.     OLEFINE  TERPENES 

The  simpler  group  in  constitution  is  that  of  the  olefine  terpenes. 
This  group  is  represented  by  terpenes  obtained  from  the  ethereal  oils  of 
lemon,  orange,  rose,  geranium,  etc.,  and  from  India  rubber  or  caoutchouc. 

Isoprene 

This  is  a  terpene  hydrocarbon  obtained  by  the  distillation  of  caout- 
chouc. It  has  the  formula  C5H8  and  on  this  account  is  termed  a  hemi- 
ter  pene,  it  being  one  half  of  CioH16  the  more  general  composition.  The 
constitution  of  isoprene  has  been  established  as  follows: 

CH2  =  C— CH  =  CH2   Isoprene  or  2-Methyl  buta  i-3-di-ene. 

CH3 

As  will  be  discussed  later  this  simple  terpene  polymerizes  in  forming 
caoutchouc  and  becomes  a  cyclic  hydrocarbon. 

Citrene  and  Derivatives 

This  compound  is  the  terpene  obtained  from  lemon  oil.  Its  con- 
stitution is  probably  CH3-C  =  CH-CH2-CH2-C  =  CH-CH3 

CH3  CH, 

Citrene 
2-6-Di-methyl  octa  2-6-di-ene 


8l6  ORGANIC    CHEMISTRY 

Geraniol,  Citral. — Citrene  by  oxidation  yields  alcohol  and  aldehyde 
products  as  follows : 

CH3— C  =  CH— CH2— CH2— C  =  CH— CH2OH 

I  ! 

CH3  CH3 

Geraniol  (alcohol) 

CH3— C  =  CH— CH2— CH2— C  =  CH— CHO 

I  I 

CH3  CH3 

Citral  (aldehyde) 

Geraniol  is  a  constituent  of  rose  and  geranium  oils  and  citral  is  in 
lemon  and  orange  oils  and  lemon-grass  oil.  When  citral  condenses  with 
acetone,  with  loss  of  water,  a  product  known  as  pseudo-ionone  is 
obtained. 

CH3— C  =  CH— CH2— CH2— C  =  CH— CH  =  (CH— CO— CH3 

I  ! 

CH3  CH3 

Pseudo-ionone 

lonone.— This  undergoes  rearrangement  with  the  formation  of  a 
compound  with  cyclic  structure  known  as  ionone  or  artificial  violet. 
H3C        CH3 

\/ 
C 


•in 


H2C 


CH— CH  =  CH— CO— CH3 

lonone 
C— CH3 

CH 

These  alcohol  and  aldehyde  compounds  have  been  previously  mentioned 
in  their  proper  place  as  unsaturated  aliphatic  compounds  (p.  170), 
but  are  referred  to  again  in  this  place  because  they  really  belong  with 
the  terpenes. 

II.  CYCLIC  TERPENES 

The  true  terpenes  according  to  chemical  constitution,  and  not 
according  to  properties  and  occurrence,  are  the  cyclic  terpenes.  These 
are  of  two  kinds,  viz. : 

A .  Mono-cyclic  terpenes. 

B.  Di-cyclic  terpenes. 


TERPENES 


8i7 


A.   MONO-CYCLIC  TERPENES 

The  mono-cyclic  terpenes,  as  the  name  indicates,  have  the  struc- 
ture of  a  single  cycle  or  ring  of  hydrogen-carbon  groups. 

Cymene. — When  heated  with  iodine  or  with  sulphuric  acid  some  of 
the  cyclic  terpenes,  e.g.,  pinene,  yield  the  benzene  hydrocarbon  cymene, 
i -methyl  4-isopropyl  benzene  (p.  492).  All  of  the  cyclic  terpenes 
have  been  shown  to  be  hydro genated  derivatives  of  cymene.  These 
hydrogenated  cymenes  are  of  different  groups  depending  on  whether 
two,  four  or  six  hydrogen  atoms  have  been  added.  These  hydrocar- 
bons and  their  relationship  to  cymene  are  repesented  by  the  following 
formulas. 


CH; 


CH3 


CT ( 

k>CH     ( 


CH 


+  2H)        HCi^  ^SCH 

-2H)         HcL  JcH 


CH 


ICH      (— 2H) 


CH 

/\ 
H3C        CH3 

Cymene 


i  -Methyl  4-iso- 
propyl benzene 


CH 


H3C        CH3 

Di-hydro  cymene 


Terpa-di-ene 
Mentha-di-ene 


(  +  2H) 
(-2H) 


CH 

/\ 
H3C        CH3 

Tetra-hydro  cymene 


CH3 

I 
CH 


CH 

I 
CH 


H3C        CH3 

Hexa-hydro  cymene 


Terpene 
Menthene 


Terpane 
Menthane 


r,2 


8i8 


ORGANIC    CHEMISTRY 


MEN THANE  GROUP 


The  first  group  of  mono-cyclic  terpenes  is  known  as  the  men- 
thane  group  from  the  name  of  the  fully  hydrogenated  compound 
hexa-hydro  cymene  which  is  therefore  considered  as  the  mother  terpene. 
This  compound  is  a  saturated  alicyclic  or  cyclo-paraffin  compound  while 
cymene  is  a  benzene  compound  containing  three  double  bonds.  In 
passing  from  the  hexa-hydro  compound  to  the  benzene  compound  by  the 
loss  of  two  hydrogen  atoms  at  each  step  the  compounds  become  more 
and  more  unsaturated  as  indicated  by  the  presence  of  first  one  double 
bond,  then  two  and  finally  three.  The  names  given  to  the  different 
compounds  indicate  this  saturated  or  unsaturated  condition.  The 
saturated  hexa-hydro  compound  is  known  as  menthane  or  a  terpane, 
the  termination  ane  being  the  same  as  in  the  case  of  the  saturated  ali- 
phatic hydrocarbons,  the  methane  series. 

MENTHENE  GROUP 

The  tetra-hydro  cymene  containing  one  double  bond  or  ethylene 
group  is  known  as  menthene  or  a  terpene,  while  the  di-hydro  cymene 
containing  two  double  bonds  is  named  mentha-di-ene,  a  terpa-di-ene. 
The  terminology  and  its  significance  will  be  recognized  as  exactly  the 
same  as  used  in  the  naming  of  the  unsaturated  aliphatic  hydrocarbons 
(p.  161). 

Isomerism. — From  an  examination  of  the  above  formulas  it  will  be 
seen  that  the  positions  occupied  by  the  added  hydrogen  atoms  in  the 
original  cymene  molecule  or,  what  is  the  same  thing,  the  positions 
occupied  by  the  double  bonds,  makes  isomerism  possible  both  in  the 
tetra-hydro  cymenes  or  menthenes  with  one  double  bond  and  the  di- 
hydro  cymenes  or  mentha-di-enes  with  two  double  bonds.  In  the 
former  case  six  isomers  are  possible  while  in  the  latter  there  are  four- 
teen. This  will  be  clear  if  we  give  the  skeleton  formulas  for  the  six 
possible  menthenes. 


Isomeric  Menthenes 


TERPENES 

As  each  of  these  menthenes  will  yield  isomeric  mentha  di-enes  the  num- 
ber of  isomers  possible  in  this  group  is  still  larger.  That  is,  one  men- 
thane  yields  six  menthenes  and  these  a  larger  number,  viz.,  fourteen, 
mentha-di-enes.  Furthermore,  stereo-isomerism  with  accompanying 
optical  activity,  due  to  the  presence  of  asymmetric  carbons,  increases  the 
number  of  possible  isomers.  It  will  not  be  necessary  to  dwell  further 
upon  the  isomerism  of  the  terpenes  it  being  necessary  simply  to  explain 
the  fact  of  the  existence  of  structural  isomers  and  of  stereo-isomers  with 
optical  activity.  The  system  of  nomenclature  of  the  isomers  will  not 
be  considered.  Reference  to  larger  books  will  be  necessary  to  make 
this  plain. 

In  regard  to  menthane,  the  saturated  hexa-hydro  cymene,  nothing 
further  need  be  said  in  regard  to  the  hydrocarbon  itself.  It  is  not  a 
natural  product  but  has  been  made  synthetically  by  hydrogenating 
cymene.  Its  oxidation  products  which  are  natural  compounds  will 
be  discussed  presently.  Of  the  menthene  hydrocarbons  also  we  need 
not  say  anything  further. 

MENTHA-DI-ENE  GROUP 
Limonenes,  Terpinenes,  Etc. 

The  most  important  group  of  the  mono-cyclic  terpenes  is  the  di- 
hydro  cymene  group  the  members  of  which  are  known  as  terpa -di-enes 
or  mentha-di-enes  with  the  composition  CioHi6  which  has  been  men- 
tioned before  as  the  unit  terpene  formula.  Several  of  the  hydrocarbons 
of  this  group  are  natural  products  in  essential  oils. 

d-1-Limonene,  Di-pentene. — The  one  occurring  most  commonly  is 
limonene,  the  inactive  variety  of  which,  designated  as  d-1-limonene,  is 
known  by  other  names,  cinene,  di-pentene  and  terpa-di-ene.  It  is 
present  in  Russian  and  Swedish  turpentine,  in  pine  needle  oil  and  in 
citronella  oil.  It  is  termed  di-pentene  because  it  results  from  the  con- 
densation of  two  molecules  of  the  pentene  known  as  isoprene  or  2 -methyl 
i-3-buta-di-ene.  It  is  obtained  together  with  isoprene  when  rubber 
is  distilled. 

d-Limonene,  Citrene. — The  optically  active  dextro  variety,  d- 
limonene,  occurs  in  various  essential  oils  and  this  has  given  to  the  com- 
pound different  names  related  to  the  source.  It  is  found  in  lemon  oil 
from  which  it  derives  the  name  citrene.  Its  occurrence  in  orange  peel 
oil  and  in  orange  blossom  oil,  known  as  neroli  oil  gives  it  the  name  hes- 


820 


ORGANIC   CHEMISTRY 


peridene.     It  is  found  also  in  cumin  oil  and  called  carvene.     It  is 
present  also  in  bergamot,  caraway  and  dill  oils. 

1-Limonene. — The  optically  active  levo  variety  1-limonene  is  pres- 
ent in  pine  needle  oil,  American  peppermint  oil,  American  spearmint 
oil  and  in  Russian  spearmint  oil. 

Terpinenes,  Phellandrene,  Sylvestrene. — Other  less  common  terpa- 
di-enes  are  the  terpinenes  found  in  cardamon  oil;  phellandrene  in  fennel 
oil  and  eucalyptus  oil  and  sylvestrene  in  Swedish  and  Russian  turpentine 
and  in  pine  needle  oil.  Sylvestrene  differs  from  the  other  terpenes  that 
have  been  given  in  that  it  is  a  derivative  of  meta-cymene,  i -methyl 
3-isopropyl  benzene,  and  not  of  para-cymene.  The  structural  formulas 
of  the  above  terpa-di-enes  are  as  follows: 

CH3  CH3  CH3 


H2C 


CH 


H2cL  J 

CH 


H3C       CH2 

Limonene 

Di-pentene 

CH3 


C 
HcX^^|CH 

H2cL       JCH 

CH 


CH 


H3C      CH3 

u-Phellandrene 


H3C       CH3 

fl-Phellandrene 


C 

/\ 

H3C       CH2 

Sylvestrene 
(from  m-cymene) 


TERPENES 


821 


The  proofs  for  the  constitution  in  the  case  of  limonene  will  be  discussed 
later  (p.  834). 

B.  DI-CYCLIC  TERPENES 

The  di-cyclic  terpenes  are  like  the  mono-cyclic  terpenes  in  their 
derivation  from  cymene  and  in  their  general  properties  and  occurrence. 
They  differ,  however,  as  their  name  indicates,  in  containing  two  cyclic 
groups  of  carbons.  One  cyclic  group  is  the  original  benzene  ring  of 
cymene.  The  second  results  from  the  linkage  of  the  isopropyl  radical 
of  cymene  to  a  second  carbon  of  the  benzene  ring. 

As  in  the  mono-cyclic  terpenes  so  in  the  di-cyclic  there  are  the  three 
groups  of  compounds  depending  on  whether  two,  four  or  six  hydrogen 
atoms  are  added  to  the  cymene.  We  have  therefore  di-cyclic  terpenes 
derived  from  hexa-hydro  cymene  in  which  there  is  no  double  bond, 
those  derived  from  tetra-hydro  cymene  in  which  one  double  bond  is 
present  and  those  derived  from  di-hydro  cymene  in  which  there  are 
two  double  bonds.  In  addition  to  these  sub-groups  we  have  three  new 
groups  differing  in  the  character  of  the  second  or  smaller  carbon  cycle. 
Taking  for  illustration  the  hexa-hydro  cymene  compounds  which  are 
saturated,  the  names  ending  in  ane,  these  groups  and  their  formulas 
are  as  follows: 


H2C 


CH 


CH 

Carane 
Carane  Group 


H2C 


Pinane 
Pinane  Group 


822 


H2C 


CH2 


CH 

Camphane 
Camphane  Group 

These  three  groups  represent  all  of  the  possible  structurally  isomeric 
arrangements  of  such  a  di-cyclic  compound.  In  carane  there  is  present 
a  hexa-methylene  ring  and  a  tri-methylene  ring.  In  pinane  there  is  a 
hexa-methylene  ring  and  a  tetra-methylene  ring,  and  in  camphane  a  hexa- 
methylene  ring  and  a  penta-methylene  ring.  While  the  saturated  mono- 
cyclic  terpenes,  the  terpanes  or  menthanes,  have  the  composition  doH20, 
the  saturated  di-cyclic  terpenes,  above,  have  the  composition  CioHis, 
the  two  hydrogens  lost  being  due  to  the  second  ring  formed  with  the 
isopropyl  group. 

Carane,  Thujene 

Carane,  the  saturated  di-cyclic  terpene  containing  a  tri-methylene 
group,  is  not  known.  An  oxygen  derivative  is  known  but  we  need  not 
consider  it.  In  the  unsaturated  groups  we  find  a  terpene,  thujene,  with 
one  double  bond  corresponding  to  menthene  but  which  has  a  tri-methylene 
group  also.  This  three  carbon  group,  however,  does  not  include  the 
isopropyl  radical  but  consists  of  three  of  the  benzene  ring  carbons. 
CH3 


H 
H2 


CH 


Thujene 


CH 

/\ 
H3C      CH3 


TERPENES 


823 


Pinane,  Pinene 

Similarly  pinane,  the  saturated  di-cyclic  terpene  containing  a  tetra- 
methylene  group,  is  not  a  natural  product  but  the  corresponding 
unsaturated  terpene  with  one  double  bond  analogous  to  menthene  is 
the  chief  constituent  of  turpentine.  It  is  known  as  pinene  and  has  the 
following  constitution. 

CH;i 


HC 


CH, 


H,C— C 


Pinene 


H2C 


CH, 


CH 


It  is  a  characteristically  smelling  liquid  boiling  at  156°  and  exists 
in  the  dextro,  levo  and  inactive  forms.  The  dextro  variety,  d-pinene, 
is  found  in  American,  Australian,  Algerian  and  Greek  turpentine  and 
the  levo  variety,  1-pinene,  in  Venetian,  French  and  Spanish  turpentine. 
Being  an  unsaturated  compound  with  one  double  linkage  it  unites  with 
hydrogen  chloride  forming  an  addition  product  known  as  pinene  hydro- 
chloride. 

Pinene  Hydrochloride.  Imitation  Camphor. — This  substance  has 
an  odor  similar  to  camphor  and  it  is  known  as  imitation  or  artificial 
camphor  but  it  is  not  synthetic  camphor.  When,  however,  pinene 
hydrochloride  is  treated  with  alcoholic  potassium  hydroxide  a  rear- 
rangement takes  place  followed  by  hydrolysis  and  a  terpene  alcohol 
is  obtained  known  as  Borneol. 

Synthetic  Camphor. — This  by  oxidation  yields  real  camphor,  i.e., 
the  synthetic  compound.  This  synthesis  will  be  explained  in  detail 
a  little  later. 

Camphane,  Camphene,  Bornylene 

The  most  important  di-cyclic  terpenes  belong  to  the  camphane 
group  in  which  a  penta-methylene  ring  is  present.  This  five  carbon 


824 


ORGANIC    CHEMISTRY 


ring  results  from  the  linkage  of  the  isopropyl  radical  to  the  para  carbons 
of  the  benzene  ring.  Camphane  itself  is  a  white,  volatile,  crystalline 
compound,  m.p.  154°,  b.p.  160°.  Three  corresponding  unsaturated 
terpenes  with  one  double  bond  are  known.  They  are  Bornylene, 
camphene  and  fenchene.  All  of  these  have  the  same  ring  structure  as 
camphane,  the  isopropyl  radical  linking  the  two  para  carbons  of  the 
benzene  ring,  thus  forming  the  second  ring  of  five  carbons.  Until 
recently  the  formula  given  below  for  Bornylene  was  assigned  to  cam- 
phene. Now,  however,  it  is  accepted  as  the  true  formula  for  Bornylene 
and  the  formula  for  camphene  is  still  in  doubt  though  the  second  one 
has  been  suggested. 


H2C 


H2C 


CH 


H2C 


CH2 

Camphene  (?) 


CH2 

Fenchene 


TERPENE  ALCOHOLS  AND  KETONES  825 

Camphene  is  a  solid  terpene.  The  dextro  variety  d-camphene  is  found 
in  camphor,  ginger  and  spike  oils,  and  the  levo  variety,  1-camphene  is 
in  citronella  and  valerian  oil  and  in  French  and  American  turpentine. 
Bornylene  does  not  occur  in  nature  but  has  been  prepared  from  the  alcohol 
corresponding  to  it  known  as  Borneol  or  Borneo  camphor.  This,  as 
previously  stated,  may  be  prepared  from  pinene  so  that  Bornylene  itself 
may  be  made  from  pinene.  Fenchene,  also,  is  not  found  in  nature  but 
is  obtained  by  reduction  of  fenchone  a  terpene  ketone  found  in  fennel 
oil  and  in  Thuja  oil. 


OXIDATION  DERIVATIVES  OR  CAMPHORS 

The  hydrocarbons  of  the  various  groups  which  we  have  just  dis- 
cussed are  the  true  terpenes.  On  oxidation  these  yield  alcohol  and 
aldehyde  or  ketone  derivatives.  The  olefine  terpenes,  only,  yield 
aldehydes  that  occur  as  constituents  of  natural  products  known  as 
essential  oils  (p.  840).  The  derivatives  of  both  groups  of  cyclic  ter- 
penes which  are  present  in  essential  oils  and  plant  gums  and  resins  are 
either  secondary  alcohols  or  ketones.  Among  these  latter  are  the  cam- 
phors of  which  common  camphor  is  the  most  important  and  best  known 
example.  In  a  general  sense  all  of  the  oxidation  products  of  the  cyclic 
terpenes  are  termed  camphors. 

MONO-CYCLIC  DERIVATIVES 
Menthol,  Menthone,  Etc. 

From  Menthane. — Taking  up  these  compounds  in  the  same  order 
in  which  we  considered  the  terpenes  themselves  we  have  first  the  alco- 
hols and  ketones  derived  from  menthane,  the  saturated  mono-cyclic 
terpene.  The  more  common  alcohol  is  known  as  menthol,  menthanol 
or  terpanol  and  the  corresponding  ketone  is  named  similarly  menthone, 
menthanone  or  terpanone.  Both  of  these  compounds  are  present  in 
Japanese,  Russian  and  American  peppermint  oil  the  former  occurring 
both  as  the  free  alcohol  and  as  the  acetic  acid  ester.  Menthol  is  a 
crystalline  solid,  m.p.  42°,  b.p.  213°.  It  has  the  characteristic  pepper- 
mint odor  and  is  used  as  a  disinfectant  and  as  a  mild  anesthetic  for 
headache.  Menthone  is  a  liquid,  b.p.  207°.  The  constitution  of  both 
compounds  is  proven  by  their  relationship  to  thymol,  i -methyl  3- 


826 


ORGANIC    CHEMISTRY 


hydroxy  4-iso-propyl  benzene  (p.  615).  Menthone  yields  mentho 
by  reduction  and  menthol  by  loss  of  six  hydrogen  atoms  is  converted 
into  thymol.  The  formulas  showing  these  relationships  are: 


CH 


H2cLJc  = 
CHJ 

CH 

/\ 
H3C       CH3 

Menthanone  j 
Menthone 


(  +  H2) 


CH, 

I 
CH 


(-6H) 


CH— OH 


CH 

I 
CH 

/\ 
H3C      CHa 

Menthanol 
Menthol 


H3C      CH3 

Thymol 


Carvo-menthol,  Carvo-menthone. — Isomeric  with  menthol  and 
menthone  are  two  other  compounds  known  as  carvo-menthol  and 
carvo-menthone.  The  constitution  of  these  two  is  proven  like  the 


tERPENE  ALCOHOLS  AND  KETONES  827 

above  by  their  conversion  into  carvacrol  (see  p.  615)  which  is  I -methyl 
2-hydroxy  4-iso-propyl  benzene.     The  formulas  are: 


CH-OH 


CH3      CH3  H3C       CH3  H3C       CH 

Carvo-menthone  Carvo-menthol  Carvacrol 


Terpin.  Terpin  Hydrate.  Cineol.  —  In  addition  to  these  mono- 
hydroxy  derivatives  there  is  another  important  one  which  is  a  di- 
hydroxy  menthane  known  as  terpan-di-ol  or  terpin.  Terpin  boils  at 
258°  and  readily  forms  a  crystalline  hydrate,  terpin  hydrate,  which 
melts  at  117°.  It  also  loses  water  yielding  an  anhydride  known  as 
cineol.  Terpin  and  terpin  h\drate  are  obtained  from  the  terpenes  in 
oil  of  turpentine  by  the  action  of  acids.  Cineol  is  found  in  eucalyptus 
oil.  The  constitution  of  these  compounds  is  proven  by  their  relation 
to  geraniol  (p.  167).  When  treated  with  5  per  cent  H2SO4  two  molecules 
of  water  are  added  to  geraniol  and  terpin  hydrate  is  formed.  This  by 
loss  of  one  molecule  of  water  forms  a  closed  ring  yielding  terpin  and  this 
by  loss  of  another  molecule  of  water  yields  cineol.  These  relationships 
are  as  follows: 

CH3—  C  =  CH—  CH2—  CH2—  C  =  CH—  CH2OH       Geraniol 

I  I 

CH3  CH3 


828 

CH3 

I 
C 

/\ 
H2C       CH 


ORGANIC   CHEMISTRY 
CH3 


.(  +  2H— OH) 


C— OH 
/\ 
H2C       CH# 


(-H— OH) 


H2C       CH2— OH 

\ 
CH 


H3C       CH3 

Geraniol 


H2C       CH2— (OH      (+  H— OH) 

\ 
CH(# 

C— OH 

/\ 

H3C       CH3 

Terpin  hydrate 


CH3 

C—  (OH 

/\ 

H2C       CH2 


H2C       CH2 

v 

CH 
C—  O(H 


CH3 


-(H— OH) 


/\ 
H2C       CH2 

I      !    o 

H2C       CH2 ' 

\/ 
CH 


H3C       CH3 

Terpin 
Terpan-di-ol 


/\ 

H3C       CH3 

Cineol 
Eucalyptol 


Terpineol,  Etc. 

Derivatives  of  Menthene. — -The  most  important  alcohols  and 
ketones  derived  from  the  menthene  unsaturated  group  of  terpenes 
are  terpineol,  di-hydro  carveol,  di-hydro  carvone  and  pulegone. 
The  first  one,  the  alcohol  terpineol)  occurs  in  its  dextro  form  in  carda- 
mon  oil  and  marjoram  oil,  in  its  lew  form  in  neroli  oil  and  in  its 
inactive  form  in  cajeput  oil.  The  constitution  is  proven  by  Perkin's 
synthesis  from  A  3-tetra-hydro  para-toluic  acid  by  means  of  the 
Grignard  reaction. 


TERPENE  ALCOHOLS  AND  KETONES  820 

jgj  CH3 

C  ' 

c  r 

/v 

Grignard  reaction 

H2C      CH2     (+CH3— Mg— I) 
\/ 


As-Tetra-hydro 

para-toluic  acid  H3C         CH3 

Terpineol 
Ai-Terpen-8-ol 

This  constitution  is  supported  also  by  the  conversion  of  terpineol  into 
terpin  and  vice  versa.  When  terpin  loses  a  molecule  of  water,  not  from 
the  two  hydroxyl  groups,  as  in  the  preceding  conversion  into  cineol, 
but  in  such  a  way  as  to  leave  one  hydroxyl  group  present,  we  obtain 
terpineol. 

CH3  CH3 

C—  (OH  C 

-H—  OH) 

zzn 

—  OH) 


L  JCH2 


CH 

I 
C—  OH  C—  OH 

/\  /\ 

H3C       CH3  H3C      CH3 

Terpin  Terpineol 

Di-hydro  Carveol,  Di-hydro  Carvone.  —  ^Di-hydro  carveol,  the  other 
important  menthen-ol,  is  present  in  kummel  oil,  together  with  the 
corresponding  ketone,  di-hydro  carvone,  from  which  it  may  be  ob- 
tained by  reduction.  This  ketone  is  the  di-hydrogen  addition  prod- 
uct of  a  mentha-di-ene  ketone  known  as  carvone  which  we  shall 
presently  consider. 


83o 


ORGANIC    CHEMISTRY 


Position  of  the  Double  Bond. — Two  points  must  be  established 
in  connection  with  the  constitution  of  these  menthene  compounds, 
viz.,  the  position  of  the  hydroxyl  and  ketone  groups  and  the  position  of 
the  double  bond.  Both  of  these  points  are  proven  by  the  following 
oxidation  of  di-hydro  carveol  to  i -methyl  2-hydroxy  4-carboxy 
benzene. 


CH, 


CH 
H2Crx'X  ^NCH—  OH 


H2cL  JcH2 

CH 


+  O(KMnO4) 


CH3 


\^ 

O 


C— OH 
CH 


C 

/\ 
H3C       CH2 

Di-hydro  carveol 


COOH 

i -Methyl  2-hydroxy 

4-carboxy  benzene 

ortho-Hydroxy  para-toluic 

acid 


This  oxidation  is  accomplished  by  means  of  potassium  permanga- 
nate, a  reaction  which  is  characteristic  of  compounds  containing  a 
doubly  bound  group  resulting  in  the  splitting  of  the  compound  at  the 
double  bond.  The  first  product  formed  results  from  the  addition  of 
two  hydroxyl  groups,  one  to  each  carbon  originally  doubly  linked. 
Further  oxidation  then  splits  the  compound  and  converts  the  remaining 
carbon  group  into  carboxyl.  After  the  removal  of  the  added  hydrogen 
of  the  menthene  compound  the  resulting  ortho-hydroxy  para-toluic 
acid  is  obtained.  The  position  of  the  ethylene  group  in  di-hydio  carveol 
must  therefore  be  in  the  iso-propyl  radical  as  the  tertiary  carbon  of 
this  radical  remains  as  carboxyl  in  the  resulting  toluic  acid.  Also  the 
hydroxyl  group  in  the  di-hydro  carveol  must  be  in  the  ortho  position 
to  the  methyl  group  and  meta  to  the  iso-propyl  group.  The  entire 
constitution  is  thus  established  and  as  di-hydro  carvone  is  the  ketone 
corresponding  to  di-hydro  carveol  the  constitution  of  the  former  is 
likewise  proven.  The  position  of  the  hydroxyl  and  ketone  groups  in 
these  two  compounds  is  also  proven  by  the  fact  that  they  each  yield 
carvacrol  or  hydroxy  cymene  in  which  the  hydroxyl  group  is  ortho  to 


TERPENE  ALCOHOLS  AND  KETONES 


831 


methyl  and  meta  to  iso-propyl.  The  formula  of  di-hydro  carvone  is 
given  below  together  with  that  of  the  other  menthene  ketone  known  as 
pulegone. 


H2C 


H2C 


C  =  0 


CH 


H3C       CH2 

Di-hydro  carvone 


H3C      CH3 

Pulegone 


Pulegone. — Pulegone  is  present  in  pennyroyal,  Mentha  pulegium. 
It  yields  menthone  by  addition  of  two  hydrogens,  which,  by  reduction, 
yields  menthol,  and  this,  by  loss  of  hydrogen,  is  converted  into  thymol. 
The  position  of  the  ketone  group  is  thus  proven. 


Carvone 

Mentha-di-ene  Ketones. — Among  the  terpene  hydrocarbons  the 
most  numerous  and  most  important  members  belonged  to  the  mentha- 
di-ene  group  characterized,  it  will  be  recalled,  by  the  presence  of  two 
double  bonds.  Among  the  oxidation  products,  however,  there  is  only 
one  belonging  to  this  group  which  we  shall  mention.  This  is  a  ketone 
known  as  carvone  which  is  present  in  kummel  oil  and  in  dill  oil.  The 
relationships  of  this  ketone  'are  very  important  and  help  to  establish 
the  constitution  of  the  mentha-di-ene  hydrocarbons,  limonene,  ter- 
pineol,  etc.  (p.  820).  The  constitution  of  carvone  itself  is  proven  by 
its  relationship  to  the  menthene  alcohols  and  ketones.  As  the  names 
indicate,  carvone  is  related  to  di-hydro  carvone,  which  it  yields  on  the 
addition  of  two  hydrogen  atoms,  and  to  di-hydro  carveol  the  corre- 
sponding alcohol.  Also  carvone  may  be  converted  into  terpineol 
which  is  isomeric  with  di-hydro  carveol.  The  constitution  of  these  two 


832 


ORGANIC   CHEMISTRY 


TERPENE  ALCOHOLS  AND  KETONES 


833 


834  ORGANIC    CHEMISTRY 

menthene  alcohols  is  proven  as  recently  shown  (pp.  829,  830)  by  their  re- 
lationship to  derivatives  of  para-toluic  acid.  In  them  the  position  of 
the  one  double  bond  is  different,  so  that  as  carvone  yields  either  of  them, 
its  two  double  bonds  must  be  in  the  two  positions,  one  as  in  di-hydro 
carveol  and  the  other  as  in  terpineol.  Furthermore,  the  position  of  the 
ketone  group  in  carvone  must  be  the  same  as  in  di-hydro  carvone  and 
the  same  as  the  hydroxyl  group  in  di-hydro  carveol.  This  is  also  proven 
by  the  fact  that  carvone,  by  heating  with  potassium  hydroxide  or 
phosphoric  acid,  yields  a  benzene  phenol,  isomeric  with  thymol,  viz., 
carvacrol,  i  -methyl  2  -hydroxy  4-isopropyl  benzene.  Thus  the  formula 
for  carvone  is  as  given  below  with  its  relation  to  carvacrol  and 
and  to  limonene. 

CH3 


HCV^     ^iCH2  HCr         >C  =  O        KC^       ^|C— OH 

H2cLJcH2 
CH 

C 

/V 
H3C       CH2  H3C       CH2  H3C       CH3 

Limonene  Carvone  Carvacrol 

As  carvone  may  be  converted  into  limonene,  a  mentha-di-ene  hydro- 
carbon, the  constitution  of  the  two  must  agree  and  the  formula  for  the 
latter  is  as  above  which  is  the  same  as  previously  given  to  it  (p.  820). 
Limonene  is  thus  the  mother  terpene  of  carvone. 

The  preceding  tabular  scheme  of  the  mono-cyclic  terpenes  and 
their  oxidation  products  shows  the  relationships  which  we  have  been 
discussing. 


CAMPHOR 

DI-CYCLIC  DERIVATIVES 
Borneol,  Camphor 


835 


The  most  important  of  all  of  the  oxygen  derivatives  of  the  terpene 
hydrocarbons  are  those  of  the  di-cyclic  group.  Of  these  the  most 
common  is  the  well-known  substance  camphor,  also  termed  Japan 
camphor.  It  is  a  ketone  derivative  of  a  di-cyclic  terpene  of  the  cam- 
phane  type  known  as  Bornylene.  The  corresponding  alcohol  deriva- 
tive is  known  as  Borneol,  or  Borneo  camphor. 

Thujone,  Fenchone. — Two  other  ketone  derivatives  are  known, 
viz.,  thujone  and  fenchone.  They  occur  together  in  thuja  oil. 
Thujone  is  present  also  in  tansy,  wormwood  and  sage  oils  while  fen- 
chone is  found  in  fennel  oil.  Without  taking  up  the  proofs  for  the 
constitution  of  these  two  ketones  we  may  give  their  formulas  as 
below: 


H2C 


CH2 

Fenchone 

They  are  derivatives  of  saturated  di-cyclic  terpenes  which  in  turn  are 
related  to  the  unsaturated  di-cyclic  terpenes  thujene  and  fenchene 
which  we  have  previously  discussed  (p.p.  822,  824). 

Constitution  of  Camphor. — The  constitution  of  camphor  and  of 
Borneol  has  been  established  by  Kompa's  synthssis  of  camphoric  acid 
which  is  obtained  by  the  oxidation  of  camphor. 

Kompa's  Synthesis  of  Camphoric  Acid.— The  synthesis  of  camphoric 
acid  is  accomplished  by  starting  with  di-ethyl  oxalate  and  condensing 
it  with  the  di-ethyl  ester  of  di-methyl  glutaric  acid. 


836 
CO(OR 


CO(OR 

Di  -ethyl 


ORGANIC  CHEMISTRY 

H)CH— COOR 

(CH3)— C— (CH8)         > 


oxalate 


H)CH— COOR 

Di-ethyl  di-methyl 
glutarate 


II 


CO C— COOR 

I 
H3C— C— CH3 


CO CH— COOR 

Di-keto  di-ethyl 
apo -camphorate 


C— 


•  CH3 

I 
CO  ---  C—  COOR 

CH3—  C—  CH3 


CO  ---  CH—  COOR 

Di-keto  di-ethyl 
camphorate 


CH3 

I 

-c— 


c=o 


H3C— C— CH3 


H3C— C— CH3 


CH< 


— COOH 


Camphoric  acid 


Camphor 


Thus  camphor,  writing  the  formula  as  a  terpene,  has  the  following 
formula  and  Borneol  that  of  the  corresponding  alcohol. 


CH3 

i 
C 


H2C 


H2C 


H3C— C— CH. 


H2C 


(+H) 
(+0) 


CH2 


C 
H 

Camphor 


CHOH 


CH2 


Borneol 


CAMPHOR 


837 


CHa 

I 
C 


H2C 


CH 


H3C— C— CHa 


H2C 


CH 


C 
H 

Bornylene 

Camphor  and  Borneol  are  therefore  derived  from  a  camphane  di-cyclic 
terpene  in  which  the  isopropyl  group  joins  the  para  carbons.  The 
unsaturated  di-cyclic  terpene  corresponding  to  camphor  was  at  first 
supposed  to  be  camphene  but  later  work  has  proven  that  it  is  not 
camphene  but  Bornylene  which  has  the  structure  corresponding  to 
camphor.  The  constitution  of  camphene  is  still  unestablished. 

Synthesis  of  Camphor. — The  relationship  of  camphor  to  pinene,  the 
terpene  present  in  turpentine,  is  of  especial  interest  and  importance 
in  connection  with  its  synthesis.  Pinene  is  the  unsaturated  di-cyclic 
terpene  related  to  the  saturated  di-cyclic  terpene  pinane  (p.  823).  In 
both  of  these  terpenes  the  di-cyclic  arrangement  is  different  from  that 
in  camphane  and  Bornylene  in  that  the  isopropyl  group  in  forming  the 
secondary  cycle  joins  the  meta  carbons  instead  of  the  para.  Now 
pinene,  by  addition  of  hydrogen  chloride,  forms  a  hydrochloride  which 
has  been  referred  to  as  artificial  camphor.  This  hydrochloride  is 
identical  with  the  hydrochloric  acid  ester  of  Borneol  and  may  be  con- 
verted into  Borneol  by  hydrolysis.  Now  as  Borneol  can  be  oxidized 
to  camphor  we  may  thus  obtain  true  synthetic  camphor  from  pinene. 
The  reactions,  involving  an  intermediate  product  and  then  rearrange- 
ment of  the  secondary  cycle  in  pinene,  are  as  follows: 


CHC1 


H2C 


Pinene 

(From  Turpentine) 


Pinene  hydro  - 
chloride 
Bornyl  chloride 

+  KOH 

Hydrolysis 

+  HC1 

esteri- 
fication 

H2C 


H2 


+  0 


H2C 


H2C 


CHOH 


CH2 


These  reactions,  in  principle,  are  those  used  in  the  commercial  synthesis 
of  camphor  and  show  the  relationship  of  the  intermediate  products. 
The  details  of  the  methods  actually  used  are  various  and  may  be  found 
by  consulting  larger  books.  The  pinene  is  obtained  from  turpentine, 
the  turpentine  itself  being  used  directly.  The  production  of  synthetic 
camphor  from  this  source  has  been  developed  very  much  during  recent 
years. 

Natural  Camphor. — Camphor  is  obtained  as  a  natural  product 
from  the  camphor  tree,  Laurus  camphor  a  (or  Cinnamomum  camphor  a). 


TURPENTINE  AND  ESSENTIAL  OILS  839 

which  grows  chiefly  in  Japan,  China  and  Formosa.  It  is  obtained 
from  trees  30-40  years  old,  being  present  in  the  wood  somewhat  simi- 
larly to  turpentine  in  pines.  Being  a  solid  instead  of  a  liquid  it  must 
be  extracted  from  the  wood  with  boiling  water,  or  by  distillation  with 
steam.  On  cooling  the  hot  water  extract  or  distillate  the  camphor 
separates  as  a  white  crystalline  mass.  This  crude  product  is  refined 
by  heating  it  with  charcoal  and  lime  when  pure  camphor  sublimes.  It 
is  a  white,  bitter,  rather  soft  crystalline  substance,  melting  at  178° 
and  boiling  at  207°,  but  subliming  slowly  at  ordinary  temperatures. 
Borneol  or  Borneo  camphor  is  the  corresponding  alcohol.  It  is  very 
similar  to  camphor  in  its  properties. 

In  1907  about  4,300,000  kilos  of  camphor  were  produced  in  Japan 
and  Formosa  where  the  industry  is  a  state  monopoly.  New  planta- 
tions of  trees  are  planted  each  year,  some  5,000,000  being  set  out  in 
1909. 

The  world's  consumption  of  camphor  is  about  5000-6000  tons. 
Camphor  is  also  produced  somewhat  in  Italy  and  in  Florida  and  Texas. 
Most  of  the  camphor  is  utilized  in  the  manufacture  of  celluloid  (p.  376), 
about  70  per  cent  of  the  product  being  thus  used  under  normal  condi- 
tions. About  2  per  cent  is  used  in  the  manufacture  of  explosives,  to 
make  them  insensitive  to  shock;  13  per  cent  for  pharmaceutical  prepara- 
tions and  15  per  cent  for  miscellaneous  purposes.  Its  most  common 
use  is  as  an  insecticide  for  the  moth  larvae  in  which  use  it  is  largely 
replaced  by  naphthalene  in  the  form  of  moth  balls. 

Turpentine  Industry 

It  has  been  previously  stated  that  the  terpenes  as  natural  products 
are  found  in  the  essential  oils  of  various  plants  especially  conifers  and 
citrus  plants.  The  most  common  and  abundant  natural  product  of 
this  nature  is  turpentine  which  is  the  essential  oil  of  various  conifer 
trees,  certain  pines,  firs  and  larches.  Turpentine  is  also  termed  Ameri- 
can, French,  Venetian,  etc.,  according  to  the  locality  of  growth.  The 
turpentine  is  obtained  from  the  tree  by  cutting  incisions  and  collecting 
the  juice.  In  some  cases  the  wood  is  cut  up  and  distilled  directly. 
Crude  turpentine  becomes  resinous  on  standing.  On  distilling  the 
crude  product  with  steam  pure  turpentine  or  oil  of  turpentine  (essence 
of  turpentine)  passes  over  leaving  behind  a  solid  resin  known  as  rosin 
or  colophony.  Pine  oil  of  turpentine  is  a  clear,  colorless  liquid  of 


840  ORGANIC  CHEMISTRY 

characteristic  odor.  It  boils  at  156°  but  readily  volatilizes  in  the  air 
especially  when  spread  in  a  thin  layer.  On  standing  in  the  air  it 
resinifies  somewhat.  It  is  a  good  solvent  of  resins,  rubber,  phosphorus 
and  sulphur.  Its  principal  use  is  in  varnishes  and  paints.  In  both 
varnishes  and  paints  the  turpentine  is  used  as  a  thinning  agent. 
Varnishes  consist  of  various  resins  (copal,  rosin,  shellac)  dissolved  in  oil, 
which  acts  as  dryer,  and  this  mixture  is  thinned  with  turpentine.  In 
paints  various  pigments  are  similarly  dissolved  in  drying  oils  and 
thinned  with  turpentine.  When  spread  in  a  thin  layer  the  turpentine 
readily  evaporates  leaving  the  resin  of  the  varnish  and  the  pigment  of 
the  paint  spread  in  a  thin  layer  mixed  with  the  drying  oil  which  on 
oxidizing  forms  a  hard  smooth  surface  coating.  Rosin  or  colophony 
.varnishes  are  poor  in  quality  compared  with  those  made  from  copal 
resin.  Shellac  or  lac,  a  resin  obtained  from  certain  Indian  trees,  is 
used  chiefly  dissolved  in  methyl  alcohol  as  a  spirit  varnish.  The 
principal  terpene  in  turpentine  is  pinene.  As  this  is  optically  active, 
the  turpentine  itself  is  dextro  or  levo  according  to  which  pinene  pre- 
dominates. United  States,  France,  England,  Germany  and  Russia 
are  the  principal  countries  producing  it.  In  1909  there  were  1585 
turpentine  distilleries  in  the  United  States  producing  about  580,000 
barrels  valued  at  about  $25,000,000  and  in  1911  the  United  States 
exported  about  18,000,000  gallons.  One  cubic  meter  of  fir  yields  10 
kilos  of  crude  turpentine  which  in  turn  yields  7  kilos  of  rosin  and  3 
kilos  of  oil  of  turpentine.  One  cubic  meter  of  pine  yields  22  kilos  of 
crude  turpentine  yielding  16  kilos  rosin  and  6  kilos  of  oil  of  tur- 
pentine. Larch  yields  between  these  two. 

Rosin — Colophony. — The  solid  resin  left  as  a  residue  when  crude 
turpentine  is  distilled  is  known  as  rosin  or  colophony.  It  is  a  hard, 
brittle  resin,  too  brittle  to  make  a  good  varnish.  The  chief  uses  of 
rosin  are  in  soap  making  (resin  soaps),  varnishes,  sealing  wax  and  in 
sizing  paper.  Sealing  wax  is  a  mixture  of  rosin,  shellac,  turpentine 
and  mineral  substances  such  as  chalk,  burnt  gypsum,  kaolin,  etc. 

ESSENTIAL  OILS  AND  PERFUMES 

In  the  preceding  discussion  of  the  terpenes  we  have  frequently  re- 
ferred to  essential  oils  or  as  they  are  also  termed  ethereal  oils.  These 
names,  however,  do  not  apply  to  a  distinct  chemical  group  of  com- 


TURPENTINE  AND  ESSENTIAL  OILS  841 

pounds  but  to  a  group  of  products  which  are  obtained  from  plants  by 
similar  processes  of  extraction  and  which  possess  certain  general  char- 
acters in  common.  They  are  usually  more  or  l6ss  volatile,  aromatic 
substances  possessing  an  odor  which  is  often  distinctive  of  the  plant 
from  which  they  are  obtained.  Being  both  volatile  and  aromatic  they 
are  used  in  the  manufacture  of  perfumes.  The  compounds  isolated 
from  these  essential  oils  are  therefore  the  odoriferous  constituents  of 
the  flowers  and  other  parts  of  certain  plants.  These  compounds  belong 
to  various  classes,  viz. :  esters,  aldehydes,  ethers  and  ter penes,  the  latter 
including  both  the  hydrocarbons  and  their  oxidation  products.  There- 
fore, while  the  consideration  of  the  essential  oils  is  not  connected  solely 
with  the  discussion  of  the  terpenes,  yet  it  has  been  best  to  postpone 
any  general  treatment  of  the  subject  until  the  terpenes  had  been  con- 
sidered. 

Esters. — The  simplest  class  of  compounds  present  in  essential  oils 
are  the  esters  or  ethereal  salts  (p.  140).  In  our  early  discussion  of  these 
compounds  in  the  aliphatic  series  it  was  stated  that  the  odor  and  flavor 
of  common  fruits  is  probably  due  to  ester  compounds  and  that  certain 
empirical  mixtures  of  esters  are  used  as  artificial  fruit  essences.  Artifi- 
cial apple  essence,  for  example,  ma>  be  prepared  by  mixing  certain 
proportions  of  ethyl  nitrite,  ethyl  acetate  and  amyl  valerate  with 
chloroform,  aldehyde  and  alcohol.  An  example  of  an  essential  oil 
which  consists  of  a  single  ester  is  oil  of  winter  green. which  is  the  methyl 
ester  of  salicylic  acid,  ortho-hydroxy  benzoic  acid  (p.  714). 

Aldehydes. — Some  essential  oils  contain  aldehydes,  e.g.,  oil  of  bitter 
almonds,  which  is  benzaldehyde  (p.  654).  Oil  of  cinnamon  and  oil  of 
cassia  contain  mostly  cinnamic  aldehyde  (p.  656). 

Ethers. — Ethers  are  also  constituents  of  essential  oils  either  as  simple 
ethers  or  as  mixed  ether-alcohol  or  ether-aldehyde  compounds.  Ex- 
amples of  such  oils  are  oil  of  anise  containing  anis  aldehyde  and  ane- 
thole  (p.  661),  and  oil  of  clove  which  contains  eugenole  (p.  623). 

Olefine  Terpenes. — The  olefine  terpenes  and  the  alcohols  and  alde- 
hydes derived  from  them  are  found  in  several  essential  oils,  e.g.,  oil  of 
geranium  contains  geraniol  and  citronellol  (p.  167),  and  oil  of  lemon, 
citral  and  citronellal  (p.  170). 

Cyclic  Terpenes.— The  cyclic  terpenes  and  their  oxidation  deriva- 
tives such  as  pinene,  limonene,  menthol,  terpineol,  cineol,  carvone, 
fenchone  and  camphor  are  found  in  a  large  number  of  essential  oils 


842 


ORGANIC  CHEMISTRY 


such  as  turpentine,  oil  of  peppermint,  oil  of  lemon,  oil  of  caraway,  fennel 
oil,  camphor,  etc. 

The  following  table  gives  some  of  the  more  common  essential  oils 
with  their  source  and  their  chief  constituents. 

TABLE  XX.— ESSENTIAL  OILS 


Oil 

Source 

Chief  constituents 

Fruit  essences  

Oil  winter  green  
Oil  bitter  almonds  
Cinnamon  oil.               ... 

Common  fruits  

Wintergreen  
Bitter  almonds  
Cinnamon 

Mixtures  of  simple  esters  of  mono- 
basic   acids    and    mono-hydroxy 
alcohols. 
Methyl  salicylate 
Benzaldehyde 
Cinnamic  aldehyde  (Eugenole) 

Cassia  oil  

Cassia  

Cinnamic  aldehyde 

Anise  oil. 

Cinnamyl  acetate 
Anethole 

Clove  oil 

Clove 

Estragole 
Anis  aldehyde 

Geranium  oil  
Lemon  oil  

Geranium  
Lemon 

Geraniol 
Citronellol 

Limonene 

Orange  blossom  oil  (Neroli) 

Phellandrene 
Citral 
Citronellol 
Geraniyl  acetate 
Linalol 
Linalol 

Orange  oil  . 

Linalyl  acetate 
Geraniol 
Methyl  anthranilate 
Limonene 

Lemon  grass  oil  
Rose  oil 

Andropogon  citratus.  . 
Rose 

(Citral  Citronellol) 
Citral 

Peppermint  oil  

Peppermint  

Citronellol 
Geraniyl  acetate 
Menthol 

Turpentine  oil 

Menthyl  esters 
Menthone 
(Pinene,  Limonene) 

Pine  needle  oil  
Rosemary  oil  

Pine  needles  
Rosemary 

Pinene 
Sylvestrene 

Camphor 

Camphene 
Cineol 
Camphor 
Borneol 

Camphor  oil 

Borneol 

Spearmint  oil 

Phellandrene 
Dipentene 
Eugenole 
Terpineol 
Cineol 

T  inalnl 

Tansy  oil  
Ylang-vlang 

Tansy  

Carvone 
Thujone 
Camphor 
Borneol 

T  inq  Inl 

Geraniol 
Benzoic  esters 
Methyl  ester  of  p-cresol 

RUBBER  84, 

Rubber — C  aoutchouc 

Source. — The  common  substance  which  is  known  as  rubber  is  the 
product  obtained  by  the  coagulation  of  the  juice  or  latex  which  is 
present,  usually  in  the  bark,  but  sometimes  in  the  woody  tissue,  of 
certain  tropical  or  sub-tropical  trees,  shrubs  and  vines.  Gutta-percha 
is  a  variety  of  rubber  differing  in  physical  properties.  The  chemical 
individual  present  in  rubber  is  a  terpene  hydrocarbon  known  as 
caoutchouc. 

Though  rubber-yielding  plants  are  quite  widely  distributed  geo- 
graphically, the  chief  commercial  localities  are  the  Amazon  region  of 
South  America  (Para  rubber),  the  Congo  region  of  central  Africa,  and 
the  Malay  peninsula  with  the  adjoining  islands.  In  the  Amazon 
region  the  trees  are  native  or  wild,  while  in  the  Malay  States  cultiva- 
tion of  the  trees  on  large  plantations  is  practiced.  When  the  latex  is 
obtained  from  the  bark  it  is  secured  by  cutting  incisions  and  allowing 
the  juice  to  flow  out  in  much  the  same  manner  as  in  the  case  of  tur- 
pentine. The  latex  so  obtained  is  an  opaque  milky  liquid  which  con- 
sists of  a  water  emulsion  of  globules  of  pure  rubber  or  caoutchouc. 
Other  substances  such  as  proteins,  carbohydrates,  resins  and  salts  are 
also  present  either  in  solution  or  suspension. 

Coagulation  of  the  Latex. — Pure  rubber  or  caoutchouc  is  an  emulsion 
colloid  and  in  most  cases  is  held  in  emulsion  by  the  protective  action 
of  other  colloids,  principally  proteins.  The  breaking  up  of  the  emul- 
sion with  the  coagulation  of  the  caoutchouc  depends  thus  upon  the 
removal  or  destruction  of  the  protective  colloids.  This  is  accomplished 
by  different  means.  The  latex  of  the  para  rubber  from  the  Amazon  is 
coagulated  by  heat  and  smoke,  while  the  latex  from  the  same  species  of 
tree  on  the  plantations  of  the  Malay  States  is  usually  coagulated  by 
treatment  with  acid.  Boiling  of  the  latex,  the  addition  of  formalde- 
hyde, and  simple  dilution  with  water  are  other  methods  in  use.  En- 
zymes are  also  present  associated  with  the  protective  colloid  proteins 
but  their  function  seems  not  to  be  connected  with  the  coagulation  of 
the  caoutchouc. 

Properties  of  Pure  Caoutchouc. — Pure  caoutchouc  may  be  obtained 
by  dissolving  rubber  in  certain  solvents,  after  first  removing  resins 
by  solution  in  acetone.  The  rubber  free  from  resins  is  treated  with 
chloroform,  benzene,  or  carbon  tetra-chloride,  all  of  which  are  solvents 
of  caoutchouc.  Evaporation  of  the  solvent  leaves  pure  caoutchouc. 


844  ORGANIC  CHEMISTRY 

Caoutchouc  so  obtained  is  a  colorless,  transparent  hydrocarbon  of  the 
composition  C5H8  or  better  (C5H8)*.  It  is  an  emulsion  colloid  of  a 
density  approximately  0.90.  It  is  a  non-conductor  of  electricity  and  this 
is  one  of  its  important  properties.  It  takes  up  liquids  and  swells. 
It  is  moderately  resistant  to  the  diffusion  of  gases  and  can  be  used  for 
balloons  but  is  not  as  good  as  other  materials.  Pure  caoutchouc  is  a 
soft,  sticky,  gummy  mass  of  low  elasticity  and  in  this  condition  pos- 
sesses almost  no  desirable  technical  properties.  In  order  to  give  it  such 
properties  it  is  very  definitely  changed  in  the  process  of  manufacture. 

Manufacture. — The  crude  rubber  obtained  by  any  of  these  methods 
of  coagulation  contains  most  of  the  substances  previously  mentioned 
as  present  in  the  latex.  In  the  subsequent  process  of  manufacturing 
rubber  goods  some  of  these  impurities  are  partially  removed.  This 
is  accomplished  by  macerating  the^  rubber  between  rolls  in  the  presence 
of  water.  The  continual  maceration  and  washing  removes  some  of  the 
ash  constituents  and  soluble  substances  and  leaves  the  rubber  in  a 
pure  and  more  uniform  condition.  During  the  purification  process  of 
maceration  and  washing  the  rubber  is  mixed  with  certain  substances  and 
is  then  finally  subjected  to  the  treatment  known  as  vulcanization. 
The  substances  added  are  of  several  classes.  Metallic  oxides  such  as 
barium  oxide  or  zinc  oxide,  barium  sulphate  (barytes)  kaolin,  French 
chalk,  are  added  as  fillers  to  give  weight  to  the  rubber.  Colored 
sulphides  are  added  to  give  color  such  as  the  red  color  of  antimony 
rubber  due  to  antimony  penta-sulphide.  Arsenic  and  mercury  sul- 
phides are  also  used  and  likewise  red  lead  (PbaC^)  and  lead  peroxide 
(PbO2),  lead  chromate,  Prussian  blue  and  lampblack.  The  sulphides 
are  effective  also  in  the  subsequent  vulcanization.  Paraffin,  rosin  and 
tar  are  also  used.  In  addition  to  these  are  substances  added  as  vul- 
canizing accelerators,  such  as  litharge  (PbO),  calcium  hydrate  and 
magnesium  carbonate. 

Vulcanization. — The  most  important  treatment  of  rubber,  in  the 
process  of  converting  it  into  a  technically  valuable  product,  is  that 
known  as  vulcanization.  This  consists  in  the  addition  of  sulphur 
which  produces  a  very  definite  change  in  properties.  The  sticky 
or  adhesive  character  of  pure  caoutchouc  is  entirely  lost  and  it  becomes 
very  elastic  and  does  not  set  when  stretched.  Even  with  wide  range 
in  temperature  it  neither  hardens  nor  softens  and  it  becomes  insoluble 
in  caoutchouc  solvents,  The  presence  of  sulphur,  usually  in  small 


RUBBER  845 

amounts,  thus  converts  a  substance  with  almost  no  valuable  properties 
into  one  of  the  highest  importance  in  much  the  same  way  that  the  pres- 
ence of  a  small  amount  of  carbon  changes  the  properties  of  pure  iron 
into  those  of  the  valuable  product  known  as  steel. 

As  to  whether  the  addition  of  sulphur  is  a  chemical  or  physical 
change  we  shall  say  little.  Evidence  appears  on  both  sides  and  all  we 
need  say  here  is  that,  in  whichever  manner  the  sulphur  really  acts,  it 
affects  the  caoutcliouc  in  a  very  definite  way,  is  absorbed  by  it,  re- 
mains there  in  some  kind  of  union  and  is  unable  to  be  removed  by  sul- 
phur solvents.  The  amount  of  sulphur  thus  definitely  held  by  the 
caoutchouc  is  about  3  per  cent,  in  the  case  of  soft  rubber,  while  in 
hard  rubber  it  may  be  as  much  as  32  per  cent.  In  both  cases  more  than 
this  amount  of  sulpher  is  usually  present  but  the  excess  is  as  free  sul- 
phur which  may  be  removed  by  solvents. 

There  are  two  general  methods  of  bringing  about  this  union  of  sul- 
phur with  the  caoutchouc.  In  hot  vulcanization  the  sulphur  is  mixed 
with  the  rubber  in  the  process  of  maceration.  The  rubber  is  then  sub- 
jected to  heat,  i  io°-i4O°,  by  superheated  steam  in  a  closed  bath  or  under 
pressure  of  heated  plates.  Still  other  goods  are  heated  in  chambers  the 
temperature  of  which  is  raised  by  means  of  steam  pipes.  Cold  vul- 
canization is  effected  by  treating  the  rubber,  which  has  previously  had 
no  sulphur  mixed  with  it,  with  sulphur  mono-chloride,  (82012),  dis- 
solved in  carbon  disulphide  or  carbon  tetra-chloride.  The  process  of 
vulcanization  was  discovered  in  1839  by  Goodyear  in  the  United  States 
and  in  1842  by  Hancock  in  England,  both  using  the  hot  process.  The 
cold  process  was  discovered  in  1846  by  Parkes.  The  important  use  of 
rubber  technically  may  be  considered  as  dating  from  the  time  of  these 
processes. 

Constitution.  Synthesis. — The  constitution  and  synthesis  of  caout- 
chouc is  connected  with  two  of  the  terpene  hydrocarbons  previously 
mentioned.  It  has  been  stated  that  caoutchouc  is  a  hydrocarbon  of 
the  composition  (CsH8),.  As  this  is  the  formula  for  certain  of  the 
terpenes  we  should  naturally  expect  to  find  that  caoutchouc  is  itself 
a  member  of  this  group. 

Isoprene.— As  early  as  1860  it  was  found  that  caoutchouc  on  dis 
dilation  yielded  a  terpene  hydrocarbon  to  which  the  name  isoprene 
(p.  162)  was  given  by  its  discoverer  Williams,  an  Englishman.     With 
the  isoprene  another  hydrocarbon  was  also  obtained  which  was  given 


846  ORGANIC  CHEMISTRY 

different  names,  viz.,  caoutchine  and  di-isoprene.  It  was  found  to  be 
identical  with  di-pentene  (p.  819),  a  terpene  obtained  from  turpentine 
and  which  is  the  inactive  form  of  limonene.  In  1875  Bouchaidat 
converted  isoprene  into  di-pentene  and  also  by  distillation,  after  treat- 
ment with  hydrochloric  acid  in  the  cold,  he  obtained  a  residue  practi- 
cally identical  with  caoutchouc  itself.  These  results  were  confirmed 
by  Tilden  in  1882  and  in  1884  he  obtained  isoprene  from  turpentine. 
In  1892  Tilden,  and  in  1894  Weber,  succeeded  in  obtaining  caout- 
chouc from  isoprene  made  from  turpentine  and  vulcanized  it.  Thus 
far,  however,  the  synthesis  of  caoutchouc  was  simply  from  turpentine, 
a  related  substance. 

The  synthesis  of  caoutchouc  from  other  compounds  than  the  ter- 
penes  themselves  was  made  possible  by  two  syntheses  of  isoprene  which 
established  its  constitution.  These  syntheses  were  by  Ipatiew  and 
Euler  in  1897-98.  The  synthesis  of  Ipatiew  was  from  di-methyl 
tri-methylene  di-bromide  or  di-brom  iso-pentane  which  is  2-methyl 
2-4-di-brom  butane.  The  reactions  are  as  follows  two  products  being 
obtained  one  of  which  is  isoprene  : 

CH2  =  C—  CH 


CH3 

2  -Methyl  buta 

i-3-di-ene 
CH3  >  Isoprene 

2-Methyl  2-4-di-brom 

butane 

(a-Di-methyl  tri-methylene)  I 

di-bromide 

CH3 

2  -Methyl 
buta  2-3-di-ene 

The  synthesis  of  Euler  started  with  foto-methyl  pyrrolidine  (p.  854) 
which  is  a  cyclic  imide  related  to  pyrrol  on  one  hand  and  to  succin- 
imide  on  the  other. 


HC  -  CH  H2C  -  CH2  H2C  -  CH 

II        II  II  || 

HC       CH  H2C       CH2  OC       CO 

\/  v  \y 

NH  NH  NH 

Pyrrol  Pyrrolidine  Succinimide 


RUBBER 

The    reactions  of  the  synthesis  are 
H2C— CH— CH 


H2C       CH2 

\x 

N(H 

0-Methyl 
pyrrolidine 

H2C— C— CH3 

I      II 
H2C    CH2 


847 


H2C C(H)— CH3 


+  CH3I 


'(I) 

(H)CH-C-CH3 

I         II 
CH2   CH2 


CH2  =  C— CH  =  CH2 

I 
CH3 

2 -Methyl  buta  i-3-di-ene 
Isoprene 

This  synthesis  proves  isoprene  to  be  2 -methyl  buta  i-3-di-ene. 

While  caoutchouc  was  first  obtained  by  polymerizing  isoprene  it  has 
been  found  that  other  hydrocarbons  containing  the  buta  i-^-di-ene 
group  will  likewise  yield  caoutchouc.  Such  hydrocarbons  have  been 
obtained  from  several  sources,  e.g.,  turpentine,  petroleum,  coal,  acetylene. 
Also  compounds  related  to  succinic  acid,  e.g.,  pyrotartaric  acid  (methyl 
succinic  acid)  are  possible  of  transformation  into  isoprene.  Levulinic 
acid,  which  is  aceto  propionic  acid,  CH3— CO— CH2— CH2— COOH, 
yields  a  cyclic  sulphur  compound,  methyl-thiophen  (p.  853),  which, 
like  methyl  pyrrolidine,  yields  isoprene.  Ethyl  alcohol  by  conversion 
into  acetone  and  then  by  aldol  condensation  with  ethane  yields  2- 
methyl  buta  2-ene,  CH3 — C  =  CH — CH3  which  may  be  transformed 

CH3 

into  isoprene.     Thus  the  sources  of  isoprene  and  other  hydrocarbons 
which  polymerize  to  caoutchouc  include  a  large  variety  of  substances, 


848  ORGANIC  CHEMISTRY 

such  as  carbohydrates,  so  that  the  securing  of  the  mother  terpene  for 
rubber  synthesis  is  commercially  possible. 

The  polymerization  of  isoprene  to  caoutchouc  has  been  accom- 
plished by  two  general  methods:  First  the  production  of  what  is 
termed  normal  caoutchouc  by  an  auto-polymerization  in  the  presence  of 
acid,  alkali,  amides,  urea,  etc.  Second,  the  production  of  sodium 
caoutchouc  by  polymerization  with  sodium  or  metallic  amalgams  in  the 
cold  or  by  heat.  The  different  hydrocarbons  possible  of  polymeriza- 
tion to  caoutchouc  differ  as  to  which  of  these  methods  produces  the  best 
caoutchouc  and  also  the  caoutchouc  obtained  varies  as  to  its  ability  to 
properly  vulcanize  and  yield  a  satisfactory  rubber  with  proper  physical 
properties. 

Thus  we  may  say  that  while  the  synthesis  of  isoprene  and  other 
hydrocarbons  possible  of  polymerization  into  caoutchouc  has  been 
definitely  accomplished  from  cheap  commercial  raw  materials,  and  also 
the  polymerization  of  these  hydrocarbons  into  caoutchouc  has  been 
likewise  accomplished,  together  with  the  vulcanization  of  the  synthe- 
sized caoutchouc,  yet  the  actual  production  on  a  commercial  scale  of  a 
synthetic  rubber  possessing  the  necessary  physical  properties  for  tech- 
nical use  is  hardly  an  accomplished  fact  at  present.  This  is  due,  no 
doubt,  largely  to  the  fact  that  the  valuable  properties  of  rubber  rest  not 
simply  on  the  chemical  constitution  of  the  caoutchouc  but,  in  an  even 
larger  degree,  on  the  physical  properties  of  the  substance,  which,  as  a 
colloid,  is  among  those  interesting  and  important  substances  which  we 
are  just  beginning  to  investigate  and  understand. 

In  concluding  the  discussion  of  rubber  it  may  be  well  to  give  without 
further  comment  a  suggested  constitution  for  caoutchouc  itself  as  a 
polymerized  isoprene.  The  formula  suggested  by  Harries  is  i-5-di- 
methyl  cycle  octa  di-ene. 


CH3—  C—  CH2—  CH2—  CH 


CH—  CH2—  CH2—  C—  CH 

Caoutchouc  (Harries) 


SECTION  II 
HETERO-CYCLIC  COMPOUNDS 

In  the  introduction  to  the  benzene  series  or  carbo-cyclic  compounds 
(p.  458)  the  group  of  hetero-cyclic  compounds  was  referred  to.  The  rep- 
resentatives of  this  group  which  were  mentioned  at  that  time  were  all 
direct  derivatives  of  the  open  chain  compounds.  They  included  the 
lactones,  the  lactams,  the  di-basic  acid  anhydrides  and  the  imides  cor- 
responding to  the  last,  e.g.: 

CH2— CH2— CH2— CO  Butyro  lactone,  from  7-hydroxy  buty- 

ric acid 


-o— 

CH2 — CH2 — CH2 — CO  Pyrrolidon,  lactam  of  7-amino  butyric 

acid 


CH2— CH2— CH2— CH2— CO    Piperidon,  lactam  of  5-amino  valeric 

I  acid 


OC— CH2— CH2— CO  Succinic  anhydride 

I 


-o— 

OC— CH2— CH2— CO  Succin-imide 

— NH 


All  of  these  are  derived  from  open  chain  compounds  by  the  loss  of 
water,  the  ends  of  the  chain  being  linked  together  forming  a  ring,  the 
carbon  groups  being  linked  together  by  an  anhydride  element  or  group, 
e.g.,  oxygen  or  the  imide  group.  This  ring  is  hetero-cyclic  as  distin- 
guished from  carbo-cyclic  as  in  benzene.  Also  in  uric  acid  we  have  a 
double  hetero-cyclic  compound  containing  two  urea  groups  acting  as 
the  ring  formers. 

NH— C  =  O 

/          I 
O  =  C  C— NH, 

\         ||  pC=O  Uric  acid 

'NH— C— NH7 

849 

54 


850  ORGANIC   CHEMISTRY 

Most  of  these  compounds  will  not  be  disscussed  further  as  they  have 
been  fully  treated  in  connection  with  the  open  chain  compounds  from 
which  they  are  derived.  In  all  respects  they  are  open  chain  deriva- 
tives. 

In  addition  to  these,  however,  there  are  several  other  very  impor- 
tant compounds  of  hetero-cyclic  structure  which  are  not  so  closely  re- 
lated to  the  open  chain  compounds  and  which  are  better  considered 
now  in  connection  with  others,  which  are  in  turn  directly  related  to 
benzene. 

Like  the  carbo-cyclic  compounds  the  hetero-cyclic  group  is  of  two 
types,  viz.,  those  containing  one  ring  and  those  containing  two  or  more 
condensed  rings.  The  one  ring  compounds,  furthermore,  are  of  two 
classes,  those  containing  Jive  members  in  the  ring  and  those  containing 
six. 

A.     FIVE  MEMBERED  RINGS 

The  hetero-cyclic  compounds  which  contain  jive  members  in  the  ring 
are  represented  by  three  compounds  in  one  of  which  oxygen  is  the  link- 
ing element,  in  another  sulphur  and  in  the  third  the  imide  group  (NH). 
They  are  as  follows: 

HC  -  CH  HC  -  CH  HC  -  CH 

II         I  II        II  II         II 

HC      CH  HC      CH  HC      CH 

\/  \/  \/ 

S  O  NH 

Thiophen  Furfuran  Pyrrole 

The  constitution  of  all  of  these  compounds  is  established  by  their 
syntheses  from  succinic  acid. 

Furfuran,  Furfural 

When  succin-aldehyde  (di-aldehyde)  loses  a  molecule  of  water, 
furfuran  is  obtained,  as  follows: 


CH(H)—  CH  =  (O)    -H2O    HC  =  CR.  HC  -  CH 


CH(H)—  CH  =  O  HC  =  CW  HC       CH 

Succin-aldehyde  v      / 

Furfuran          \/ 


HETERO-CYCLIC  COMPOUNDS  851 

Furfuran,  also  called  furan,  is  a  liquid  boiling  at  32°  and  is  present  in 
pine  tar.  It  is  not  important  itself  but  an  aldehyde  and  an  acid  de- 
rived from  it  are  important. 

When  pentose  sugars,  arabinose  or  xylose  or  polypentoses,  the 
pentosans,  which  are  present  in  cereal  bran  or  in  most  grasses  and  fod- 
ders, are  boiled  with  hydrochloric  acid  the  pentose  sugar  loses  three 
molecules  of  water  and  a  product  is  obtained  which  proves  to  be  the 
aldehyde  derived  from  furfuran.  This  reaction  agrees  with  the  consti- 
tution as  follows: 


(OH)  (OH) 

HC CH 

HC--CH  (-3H,0)  ||         |i 

HC        C— CHO 

H)HC   H)C-CHO  O 

Furfural 

(HO   H)0 

Pentose 

The  analytical  determination  of  pentosans  in  cattle  foods  is  based  on 
this  formation  of  furfural.  The  material  is  boiled  under  definite  con- 
ditions with  hydrochloric  acid  and  the  furfural  formed  is  distilled 
over.  The  distillate  containing  the  furfural  with  water  and  acid  is 
treated  with  phloroglucinol.  On  standing  a  black  precipitate  of 
furfural  phloroglucid  is  formed.  This  is  filtered,  dried  and  weighed 
and  the  amount  of  furfural  or  of  pentosan  present  in  the  original 
material  is  calculated  by  an  empirical  method.  Furfural  is  a  liquid 
boiling  at  162°  and  shows  distinctive  aldehyde  reactions,  being  very 
similar  in  this  respect  to  benzaldehyde.  It  undergoes  condensation  to 
form  furfuroin  just  as  benzaldehyde  does  to  form  benzoin  (p.  764). 
Furfural  on  oxidation  yields  an  acid,  pyromucic  acid. 

Pyromucic  Acid. — When  mucic  acid  is  heated  three  molecules  of 
water  and  one  of  carbon  dioxide  are  lost  and  a  monobasic  acid  is 
obtained  known  as  pyromucic  acid,  and  this  acid  by  loss  of  CO2  goes 
to  furfuran  thus  proving  it  to  be  the  acid  derived  from  furfuran.  The 
acid  is  also  obtained  by  oxidizing  furfural.  The  reactions  and  rela- 
tionships are  as  follows: 


852  ORGANIC   CHEMISTRY 

(COO)(H 

CH(OH  HC— CH 

I  (-3H— OH)  II      II 

CH(OH  — —  HC      C— COOH 

|  (-C02)  \/ 

CH(OH  ° 

Pyromucic  acid 

C(H)0(H) 

I 
COOH 

Mucic  acid 

HC— CH  HC— CH  HC— CH 

II      II  II      II  II      II 

HC     CH  HC     C— CHO          HC     C— COOH 

\/  \/  \/ 

o  o  o 

Furfuran  Furfural  Pyromucic  acid 

Furfuryl  Alcohol. — An  alcohol,  furfuryl  alcohol,  is  also  known  ob- 
tained from  the  aldehyde  by  reduction.  This  reduction  is  brought 
about  by  treatment  with  alcoholic  potassium  hydroxide,  one  molecule 
of  the  aldehyde  being  reduced  at  the  expense  of  a  second  molecule  which 
is  thereby  oxidized  to  the  acid.  Thus  one  molecule  of  pyromucic  acid 
and  one  of  furfuryl  alcohol  are  obtained  from  two  molecules  of  furfural. 

HC — CH  HC — CH  HC — CH 

II      .11  +       II      II 

HC     C— CH2OH       HC     C— COOH 

\/  \/ 

O  O 

Furfuryl  Pyromucic 

alcohol  acid 

Thiophen 

In  thiophen  the  oxygen  of  furfuran  is  replaced  by  sulphur.  Its 
name  indicates  its  occurrence  in  crude  benzene  as  obtained  from  coal 
tar.  Coal  tar  benzene  gives  a  blue  color  with  isatin  known  as  the  indo- 
phenin  reaction.  This  reaction  is  not  given  by  benzene  made  from  ben- 
zoic  acid  and  it  was  found,  by  Victor  Meyer,  to  be  due  to  the  presence 


HETERO-CYCLIC  COMPOUNDS  853 

in  crude  benzene  of  thiophen  which  he  separated  by  its  more  easy  sul- 
phonation. 

The  synthesis  of  thiophen  which  proves  its  constitution  is  from  suc- 
cinic acid  by  the  action  of  phosphorus  penta-sulphide. 

H2C— COOH  s  HC=CH 

H2C— COOH  HC=CHr 

Succinic  acid  Thiophen 

Similarly  levulinic  acid,  aceto-propionic  acid,  yields  a  methyl  homologue 
of  thiophen. 

H2C— COOH  HC=CHV 

+     -^206  I  \Q 

I  >  /** 

H2C— CO  HC-    =C 

CH3  CH3 

Levulinic  acid  Methyl  thiophen 

0-Aceto  Thiotolen 

propionic  acid 

Pyrrole 

This  five  membered  hetero-cyclic  compound  is  analogous  to  the 
two  preceding  ones  having  the  oxygen  of  furfuran  replaced  by  the 
imide  group,  ( — NH — ).  Two  methods  of  synthesis  prove  its  constitu- 
tion. Succinimide  when  distilled  with  sodium  or  zinc  dust  is  reduced 
and  pyrrole  is  obtained. 

H2C— CH2  +  H  HC— CH 

OC     CO  HC     CH 

NH  NH 

Succinimide  Pyrrole 

Similarly  succinic  aldehyde  (di-aldehyde)  by  treatment  with  ammonia 
yields  pyrrole. 

HC— CH 


HCO    CHOI          (-H20)  HC     CH 

Succinic  aldehyde  \/ 

NH 

Pyrrole 


854  ORGANIC   CHEMISTRY 

Pyrrole  is  present  in  small  amounts  in  coal  tar  but  is  obtained  in 
larger  amounts  from  the  oil  known  as  DippeVs  oil  which  is  obtained  by 
distilling  bones.  It  is  a  colorless  liquid  boiling  at  131°.  A  character- 
istic reaction  of  pyrrole  is  that  a  pine  shaving  moistened  with  hydro- 
chloric acid  is  turned  a  cherry  red  color  by  the  vapor  of  pyrrole.  This 
is  used  as  a  test  for  the  compound.  A  striking  property  of  pyrrole  is 
that  while  it  is  a  weak  base,  due  to  presence  of  the  imide  group  (NH), 
it  likewise  acts  as  an  acid,  the  hydrogen  of  the  imide  group  being  re- 
placed by  potassium.  This  potassium  compound  by  the  action  of 
chloroform  takes  up  another  carbon  and  yields  a  derivative  of  the  cor- 
responding six  membered  ring  compound  pyridine.  It  shows  its  simi- 
larity to  benzene  in  forming  substitution  products,  not  addition  prod- 
ucts, with  the  halogens.  The  tetra-iodo  pyrrole  is  an  important  anti- 
septic known  as  iodol. 

1C— CI 

Tetra-iodo  pyrrole 

1C     CI  Iodol 


NH 

All  three  of  the  hetero-cyclic  compounds  just  considered,  viz.,  furfuran, 
thiophen  and  pyrrole,  possess  definite  benzene  properties.  This  is  as 
would  be  expected  in  the  case  of  compounds  containing  a  carbon  cycle 
with  two  ethylene  groupings.  Of  the  three,  thiophen  is  the  most 
strongly  aromatic  in  its  character. 

Pyrrolidine 

By  the  action  of  nascent  hydrogen  pyrrole  takes  up  two  or  four 
hydrogen  atoms  and  is  converted  into  the  corresponding  hetero-cyclic 
compounds  containing,  in  the  first  place,  only  om  ethylene  group,  and 
in  the  second  none,  the  final  compound  being  fully  saturated.  The 
first  compound  is  known  as  pyrroline,  the  second  as  pyrrolidine. 
HC— CH  +2H  H2C— CH  +2H  H2C— CH2 

HC     CH  H2C     CH  H2C     CH2 

\/  \y  \y 

NH  NH  NH 

Pyrrole  Pyrroline  Pyrrolidine 

Pyrrolidine  may  be  synthesized  from  tetra-methylene  di-amine, 
putrescine  (p.  194),  by  the  loss  of  ammonia. 


HETERO-CYCLIC  COMPOUNDS  855 

H2C—  CH2  H2C—  CH2 

(-NH8)  I 

H2C     CH2  H2C     CH2 

J  V 

(H2N)    NH(H)  NH 

Tetra-methylene  Pyrrolidine 

di-amine 
Putrescine 

Pyrrolidine  is  also  obtained  from  succinimide  by  reduction 
H2C—  CH2  H       H2C—  CH2 


OC     CO  H2C     CH2 

v  v 

NH  NH 

Succinimide  Pyrrolidine 

All  of  these  syntheses  show  clearly  the  relationship  between  pyrrole 
and  pyrrolidine  and  confirm  the  constitution  of  pyrrole  and  of  the  other 
five  membered  hetero-cyclic  compounds. 

Proline.  —  Two  of  the  amino  acids  obtained  as  hydrolytic  cleavage 
products  of  proteins  are  derivatives  of  pyrrolidine.  They  are  proline 
and  oxyproline  (p.  392).  Proline  is  a^Aa-pyrrolidine  carboxylic  acid. 

H2C—  CH2 

Proline 
H2C     CH—  COOH  a-Pyrrolidine  carboxylic  acid 

V 

NH 

Pyrrazole,  Pyrrazoline,  Pyrrazolone 

When  pyrrole  and  pyrroline  have  one  of  their  CH  groups  replaced 
by  nitrogen,  derivatives  are  obtained  known  as  pyrrazole  and  pyrrazo- 
line.  Pyrrazoline  yields  a  ketone  known  as  pyrrazolone. 

HC—  CH  H2C—  CH  H2C—  CH 


HC      N 

H2C      N 

OC     N 

v 

x/ 

v 

NH 

NH 

NH 

Pyrrazole 

Pyrrazoline 

Pyrrazolone 

856  ORGANIC    CHEMISTRY 

Antipyrine.  —  A  di-methyl  phenyl  substitution  product  of  pyrrazo- 
lone  is  the  important  medicinal  compound  used  as  a  febrifuge  and 
known  as  antipyrine. 

HC=C—  CH3 

Di-methyl  phenyl  pyrrazolone 
OC       N—  CH3    Antipyrine 
V 


B.  SIX  MEMBERED  RINGS 
Pyridine 

The  only  six  membered  hetero-cyclic  compound  which  we  shall 
consider  is  the  one  analogous  to  pyrrole.  It  contains  a  hetero-cyclic 
ring  of  five  carbons  and  one  nitrogen  just  as  pyrrole  contains  four  car- 
bons and  one  nitrogen.  This  compound  is  known  as  pyridine.  That 
pyridine  is  a  six  membered  ring  analogous  to  pyrrole  is  proven  by  the 
fact  previously  referred  to  (p.  854),  that  potassium  pyrrole  by  the 
action  of  chloroform  takes  up  an  additional  carbon  and  yields  a  chlorine 
substitution  product  of  pyridine. 

CH 

/V 
HC  -  CH  ,    ___  _.     HC        CC1  +  KC1  +  HC1 


HC       CH  HC       CH 

\/  \/ 

NK       -.  N 

Potassium  Chlor  pyridine 

pyrrole 

The  constitution  of  pyrridine^is  established  by  numerous  syntheses- 
The  only  one  we  shall  mention  is  the  one^from  cadaverine  or  penta- 
methylenejj  di-amine.  The  corresponding  tetra-methylene  di-amine, 
as  already  stated  (p.  855),  loses  ammonia  and  yields  pyrrolidine,  the 
saturated  t  hydrogenated  pyrrole.  By  an  exactly  r  similar  reaction 
penta-methylene  di-amine  loses  ammonia  and  yields  the  saturated 
hydrogenated  pyridine  which  is  known  as  piperidine. 


PYRIDINE  AND  HOMOLOGUES  857 

CH2  CH2  CH 

XX  /\  /\ 

H2C       CH2  (-NH3  H2C       CH2  (-6H)  HC       CH 

||  »  ||  ;=:  ||        | 

H2C       CH2  H2C       CH2  (+6H)  HC      CH 

II  \/  \S 

H)NH  (NH2)  NH  N 

Penta  methylene  Piperidine  Pyridine 

di-amine 
Cadaverine 

Piperidine  by  loss  of  six  hydrogens  yields  pyridine  and  is  similarly 
made  from  pyridine  by  addition  of  six  hydrogens.  Pyridine  may  be 
considered,  therefore,  as  benzene  in  which  one  carbon  group  is  replaced 
by  nitrogen.  In  its  reaction  and  properties  pyridine  shows  its  similarity 
to  benzene.  It  acts  as  a  tertiary  base  and  like  benzene  may  be  chlori- 
nated or  sulphonated,  though  not  as  easily.  It  is  a  colorless  liquid 
boiling  at  115°,  mixing  with  water,  and  possessing  a  strong  characteris- 
tic odor.  On  this  account  it  is  used  in  its  crude  form,  mixed  with  re- 
lated compounds,  as  a  denaturant  of  alcohol.  Pyridine  is  found  in  coal 
tar  and  is  separated  from  benzene  and  other  constituents  of  light  oil  by 
treatment  with  sulphuric  acid  which  forms  the  sulphate.  It  is  also 
present  in  bone  oil  (DippeVs  oil)  together  with  pyrrole. 

Derivatives  of  Pyridine. — (i)  Hydroxy  pyridines.  These  com- 
pounds may  be  considered  as  ketone  derivatives  of  a  di-hydro  pyridine 
or  as  hydroxyl  derivatives  of  pyridine.  The  two  tautomeric  formulas 
thus  represent  them  as  follows: 


CH  CO  COH 


NH 

Hydroxy  pyridine 


(2)  Carboxylic  acids.  Of  these  pyridine  acids  there  are  mono-, 
di-,  and  tri-carboxylic  acids  known,  which  are  obtained  by  oxidation 
of  the  corresponding  mono-,  di-,  and  tri-methyl  homologues.  One  of 
the  mono-carboxylic  acids  is  known  as  nicotinic  acid  and  is  obtained 


858  ORGANIC   CHEMISTRY 

by  oxidizing  nicotine,  the  alkaloid  of  tobacco.  The  2-^-di-carboxylic 
acid  is  known  as  quinolinic  acid  and  is  obtained  by  oxidizing  quinoline 
(p.  862).  A  tri-carboxylic  acid  known  as  2-3-4  pyridine  tri-carboxylic 
acid  is  obtained  by  oxidizing  cinchonine  alkaloids. 


0 


COOH 

x%^ 
-COOH      ^      "S— COOH       r^       N— COOH 

COOH 


N  N  N 


Nicotinic  Quinolinic  2-3-4  Pyridine  tri-carboxylic 

acid  acid        .  acid 

Piperidine 

This  compound,  the  hexa-hydro  pyridine,  has  just  been  referred  to, 
and  also  previously,  in  connection  with  penta-methylene  di-amine 
(p.  194).  In  both  these  connections  its  constitution  has  been  estab- 
lished. As  its  name  indicates,  it  is  obtained  from  pepper  in  which  it 
is  present  in  amide  combination  with  an  acid  known  as  piperic  acid. 
The  compound  thus  formed  is  the  alkaloid  of  black  pepper  and  is  called 
pipeline. 

Pyridine  Homologues 

Pyridine  yields  methyl  substitution  products  which  bear  the  same 
relationship  to  it  that  toluene,  xylene  and  mesitylene  do  to  benzene. 
These  homologues  like  those  of  berizene  are  easily  oxidized  and  yield 
corresponding  carboxyl  derivatives  or  acids,  viz.,  pyridine  carboxylic 
acids,  as  just  discussed. 

Picolines. — The  three  isomeric  mono-methyl  pyridines  are  known  as 
picolines.  One  of  these  is  obtained  by  heating  strychnine  with  lime. 
From  them  by  oxidation  pyridine  mono-carboxylic  acids  are  obtained 
(p.  857). 

Lutidines.  Collidines. — The  di-methyl  pyridines  are  known  as  luti- 
dines  and  the  tri-methyl  pyridines  as  collidines. 

Conine. — One  of  the  most  important  homologues  is,  alpha-propyl 
pyridine,  which,  by  hydrogenation,  yields  alpha-propyl  piperidine 


PYRIDINE  AND  HOMOLOGTJES 


859 


which  is  the  alkaloid  conine,  the  poisonous  constituent  of  hemlock. 
The  syntheses  of  these  methyl  pyridines  are  important  in  establishing 
their  constitution  and  through  them  the  constitution  of  pyridine  itself. 
fo/a-Methyl  pyridine  is  obtained  by  distilling  acrylic  aldehyde  ammo- 
nia. This  explains  the  occurrence  of  pyridine  in  bone  oil  which  is 
obtained  by  distilling  bones  that  still  have  fat  on  them,  the  fat  yielding 
acrylic  aldehyde  or  acrolein. 

Synthesis  of  Collidine. — The  most  important  synthesis  of  pyridine 
homologues  is  that  of  collidine  from  which  pyridine  may  be  obtained 
by  elimination  of  the  methyl  groups  by  oxidation  and  loss  of  carbon 
dioxide.  When  aldehyde  ammonia  is  heated  with  aceto-acetic  ester 
a  derivative  of  a  di-hydrogenated  collidine  is  obtained,  as  follows: 

CH3 


CH(0) 


H5C2OOC— C(H2) 
H3C— C(O) 


C(H2)— COOC2H5 

C(0)— CH3 


N(H2) 
H 

Aldehyde  ammonia 

and 
Aceto  acetic  ester 


CH3 

i 
CH 

/\ 

H6C2OOC— C      C— COOC2H5 

II       II 
H3C— C      C— CH8 

\/ 

NH 

Di-ethyl  ester  of 
di-hydro  collidine 
di -car  boxy  lie  acid 

This  di-ethyl  ester  of  di-hydro  collidine  di-carboxylic  acid  is  then 
treated  with  nitrous  acid  which  removes  the  two  added  hydrogens. 
The  ester  is  then  hydrolyzed  and  carbon  dioxide  eliminated  whereby 
collidine  is  obtained.  This,  by  oxidation  of  the  methyl  groups  to 
carboxyl  groups- and  elimination  of  carbon  dioxide,  yields  pyridine. 


860  ORGANIC   CHEMISTRY 


C'H>       +HNO, 
C-CH,  (-2"> 

f 

IH 

Di-ethyl  ester  of  di-hydro 
collidine  di-carboxylic  acid 

CH3  CH3 


c 

V^      ^^C— COOC2H5                                HOOC— Cg^  ^^C— ( 

~  hydrolysis 

:1              ^^C— CH3                                              H?C— cl  ^C—( 


COOH  '•(__  2C02) 

CH  C 


g^       ^N( 

: 

l  ^^( 

^ 


(-3COQ  +0     CH3 

HOOC— cl  VC— COOH  *~ 


o 


HsC— C|,  ^  C— CHs 

N 
Collidine 

C.     CONDENSED  HETERO-CYCLIC  COMPOUNDS 

The  compounds  of  this  class  include  those  in  which  two  rings  are 
condensed  together  as  in  naphthalene.  They  differ  from  the  latter, 
however,  in  that  one  of  the  rings  is  hetero-cyclic.  This  hetero-cyclic 
ring,  with  which  the  benzene  ring  is  condensed,  may  be  either  a  five 
membered  ring,  like  pyrrole,  or  a  six  membered  ring,  like  pyridine. 
The  compounds  which  contain  a  five  membered  ring  include  indigo  and 
related  compounds.  Those  which  contain  a  six  membered  ring  are 
represented  by  a  compound  known  as  quinoline.  Because  of  the 
close  relationship  between  this  last  compound  and  pyridine,  which  we 
have  just  been  discussing,  it  is  best  to  consider  it  first-and  indigo  later. 


QUINOLINE   AND  DERIVATIVES 


86l 


CONDENSED  SIX  MEMBERED  HETERO-CYCLIC  COMPOUNDS 

Quinoline 

That  the  constitution  of  quinoline  is  that  of  a  condensed  ring  com- 
pound made  up  of  a  benzene  ring  coupled  with  a  pyridine  ring  is  shown  by 
its  synthesis  and  its  relation  to  pyridine. 

Baeyer  and  Drewsen's  Synthesis. — The  synthesis  of  Baeyer  and 
Drewsen  shows  the  constitution  the  most  clearly.  Cinnamic  aldehyde 
(p.  656)  is  C6H5— CH  =  CH— CHO.  When  the  ortho-nitro  substitu- 
tion product  of  this  compound  is  reduced  we  obtain  the  correspond- 
ing ortho-ammo  cinnamic  aldehyde.  This  by  loss  of  water  yields 
quinoline. 


-H20 


HC 


Quinoline 


cinnamic 
aldehyde 


This  proves  that  the  end  of  a  propene  three  carbon  side  chain  is  linked 
to  the  ortho  position  of  a  benzene  ring  by  means  of  nitrogen  thereby 
forming  a  hetero-cyclic  ring  coupled  to  the  benzene.  That  this  hetero- 
cyclic  ring  is  pyridine  is  proven  by  the  fact  that  when  quinoline  is  oxi- 
dized an  alpka-bela-di-carboxy  pyridine  is  obtained  which  by  loss  of 
carbon  dioxide  yields  pyridine. 


H 


0 


Quinoline 


862 


ORGANIC    CHEMISTRY 


H 


H 


HOOC—  C 


HOOC—  C 


^ 

O 

N 

Pyridine 
di-carboxylic 

acid 
Quinolinic  acid 


(-2C02) 

HC 


v^ 

O 

N 

Pyridine 


This  is  exactly  analogous  to  the  oxidation  of  naphthalene  to  ortho- 
phthalic  acid  and  the  conversion  of  this  into  benzene  (p.  689). 

Skraup's  Synthesis. — While  the  synthesis  of  Baeyer  and  Drewsen 
is  the  clearest  proof  of  the  constitution  of  quinoline  it  is  not  the  one 
most  commonly  used.  The  synthesis  most  frequently  associated  with 
the  preparation  of  this  compound  is  that  of  Skraup.  This  consists  in 
heating  together  aniline,  glycerol  and  sulphuric  acid  in  the  presence  of 
an  oxidizing  agent,  e.g.,  nitro  benzene  or  arsenic  acid.  The  glycerol 
heated  with  sulphuric  acid  loses  water  yielding  acrolein  or  acrylic 
aldehyde.  This  condenses  with  the  aniline  yielding  an  intermediate 
product  which  then  by  oxidation  loses  two  hydrogens  and  yields 
quinoline,  as  follows: 

H  H 


HC 


HC 


HC 


Acrolein 

(from  glycerol) 


(-2H) 


HC 


CH 


HC 


CH 


N 


Quinoline 


QUINOLINE  AND  DERIVATIVES 


863 


Quinoline  is  a  colorless  liquid,  b.p.  239°,  with  a  characteristic  odor. 
It  possesses  the  properties  of  a  tertiary  amine  base  forming  salts  as 
pyridine  does.  It  is  present  with  the  latter  in  coal  tar  and  in  bone 
oil  but  is  usuaUy  not  obtained  from  these  sources  being  prepared  by 
Skraup's  synthesis. 

Derivatives  of  Quinoline. — (i)  Hydroxy  quinolines.  These  are 
exactly  analogous  to  the  hydroxy  pyridines  and  like  them  are  assigned 
tautomeric  formulas. 

OH 


O 


H 
C 


HC 


HC 


CH 


CH 


or 


C 
H 


N 
H 


Hydroxy  quinoline 

Carbostyril. — If  in  the  Baeyer  and  Drewsen  synthesis  cinnamic  acid 
is  used  instead  of  cinnamic  aldehyde  the  ortho-ammo  derivative,  by 
loss  of  water,  yields  a  hydroxy  quinoline  known  as  carbostyril. 

H 

C  CH 


(-H20) 


HC 


HC 


864  ORGANIC    CHEMISTRY 

Cinchoninic  Acid. — (2)  Carboxylic  acids.  The  only  quinoline 
carboxylic  acid  of  importance  is  known  as  cinchoninic  acid  because  it 
is  obtained  by  oxidizing  cinchonine,  one  of  the  alkaloids  of  cinchona 
bark.  It  is  the  quinoline  4-carboxylic  acid  and  by  loss  of  carbon  dioxide 
yields  quinoline.  By  oxidation  cinchoninic  acid  yields  pyridine  2-3-4 
tricarboxylic  acid  (p.  858)  which  by  loss  of  carbon  dioxide  (3  mol.) 
yields  pyridine. 


H  H 

C  C 


HC 


^^>H(_CO 

— 


cl\^K^CH, 

C  N 


H 

Quinoline 


COOH 

I  H 

C  C 


X)C-C|-          >CH     (_3C02) 

HOOC— cL          JcH  HCL          J 

N  N 

Pyridine  2-3-4-  Pyridine 

tri -carboxylic 
acid 


Quinolinic  Acid. — This  acid  which  is  obtained  by  oxidizing  quinoline 
is  a  di-carboxyl  pyridine  (p.  858,  862). 

(3)  Hydrogenated  quinolines.  The  hydrogenated  quinolines  which 
are  analogous  to  piperidine,  the  hydrogenated  pyridine,  are  also  known. 
The  methyl  amino  and  ethyl  amino  derivatives  of  tetra-hydro  quinoline 
are  known  as  kairolines  and  are  antipyretics.  They  exert  a  toxic  action 
on  the  blood  corpuscles  and  are  therefore  not  used  in  medicine. 


QUINOLINE  AND  DERIVATIVES 

H  H2 

C  C 

.x\  r  ^\ 

HC,  B  §_ 

Kairoline 


]CH2 

CH2 

C 

N 

H 

1 

CH3 

The  homologues  of  quinoline  are  not  important.  An  isomeric  quinoline 
known  as  isoquinoline  has  the  nitrogen  in  the  beta  position  of  the  second 
ring. 

H  H 

HCX^^CH  J 

Isoquinoline 


^^ 


C  C 

H  H 

Isoquinoline  is  of  importance  in  its  relation  to  the  alkaloids. 

CONDENSED  FIVE  MEMBERED  HETERO-CYCLIC  COMPOUNDS 

Two  of  the  five  membered  hetero-cyclic  compounds  form  condensed 
rings  with  benzene,  viz.,  furfuran  and  pyrrole.  The  resulting  com- 
pounds are  represented  as  follows: 


CH 


866  ORGANIC    CHEMISTRY 

The  first  compound,  a  condensed  benzene  and  furfuran,  is  known  as 
cumarone  and  is  present  in  cumarone  resin.  It  is  not  of  special 
importance. 

Indole,  Oxindole,  Di-oxindole,  Isatin,  Indoxyl 

Indole. — The  second  compound  above,  a  condensed  benzene  and 
pyrrole  compound,  is  known  as  indole  and  is  a  very  important  compound 
both  physiologically  and  in  its  relation  to  indigo.  While  indigo  itself 
is  not  a  simple  condensed  hetero-cyclic  compound  it  belongs  here  in 
our  discussion  because  of  its  relation  to  indole.  The  constitution  of 
indole  is  proven  by  several  synthetic  relationships. 

Oxindole. — When  ortho-nitro  phenyl  acetic  acid  is  reduced  to  the 
ortho-amino  phenyl  acetic  acid,  the  latter,  being  a  gamma-ammo  acid, 
loses  water  yielding  a  lactam  which  is  known  as  oxindole. 


C— CH2— COOH         +H 


—  CH2—  CO(OH) 


H 

o-Amino 

phenyl 

acetic  acid 


Now  oxindole  by  reduction  with  zinc  dust  yields  indole  which  must 
therefore  have  the  constitution  as  given  below.  Oxindole  is  the  ketone 
of  a  di-hydrogenated  indole,  or  it  may  be  considered  as  the  tautomeric 
compound,  i.e.,  a  mono-hydroxy  indole. 


IN  DOLE      OXINDOLE      ISATIN      ETC. 


867 


H 

c 


C — CH 


— CH 


HC 


C—  CH 


HC 


or 


C       CH2 

V 

C  N 

H  H 

Di-hydro  indole  Oxindole 

Di-oxindole. —  Similarly  a  di-hydroxy  compound  known  as  di-oxin- 
dole  is  obtained  as  a  lactam  anhydride  from  ortho-amino  mandellic 
acid,  ortho-amino  phenyl  hydroxy  acetic  acid. 

H 

C 


— CHOH— CO(OH) 

— NH(H) 


(-H20) 


o-Amino  mandellic  acid 

H 
C 


H 
C 


CHOH 


or 


OC- 
" 


C—  OH 


C 

H 


V 

N 
H 


Di-oxindole 

Di-oxindole  yields  oxindole  by  reduction  with  tin  and  hydrochloric  acid. 


868 


ORGANIC   CHEMISTRY 


Isatin.  —  Furthermore,  a  di-ketone  derivative  of  di  -hydro  indole-  known 
as  isatin  is  prepared  from  ortho-amino  benzoyl  formic  acid  as  a  lactam 
anhydride. 

H  H 

C  C 

—  CO-CO(OH)  ^  ^SC—  CO 


NH(H) 


C 
H 

o-Amino 
benzoyl  formic  acid 


Isatin  by  reduction  with  zinc  and  hydrochloric  acid  yields  di-oxindole. 
Putting  these  compounds  together  and  showing  their  relationships 
as  indicated  by  the  syntheses  just  given,  the  constitution  in  each  case 
is  well  established. 


CH 


H 


Indole 


C  N 

H  H 

Di-hydro  indole 


+  H      (Zn  dust) 


H 
C 


C 

TT 


N 

TT 


or 


Oxindole 


+  H      (Sn  +  HC1) 


INDOLE      OXINDOLE      ISATIN     ETC. 


869 


or 


Di-oxindole 


II 

C 


+  H      (Zn  +  HC1) 


H 
C 


O 


\/ 

N 


CO 


or 


CO 


N 
H 


C  N  C 

H  H 

Indoxyl.  —  One  more  derivative  of  indole  must  be  mentioned  con- 
nected with  the  synthetic  production  of  indigo.     Isomeric  with  oxindole 
is  another  mono-hydroxy  indole  known  as  indoxyl.     It  is  prepared 
from  phenyl  glycine  ortho-caiboxytic  acid,  anthranil  acetic  acid. 
H 
C 


(-HiO) 


c—  NH—  C(H2)—  COOH 


a) 


C-(COO)H 


C  N 

H  H 

Indoxylic  acid 


Indoxyl 


870  ORGANIC    CHEMISTRY 

When  phenyl  glycine  ortho-carboxylic  acid  is  fused  with  potassium 
hydroxide  it  first  loses  water  yielding  an  acid,  indoxyllic  acid,  and 
this  loses  carbon  dioxide  yielding  indoxyl.  In  indoxyl  the  hydroxyl 
group  is  in  the  3-position  while  in  the  isomeric  oxindole  it  is  in  the  2-posi- 
tion.  All  of  these  compounds  are  thus  condensed  hetero-cyclic 
compounds  of  a  benzene  ring  and  a  pyrrole  ring.  Indole  is  the  mother 
substance  and  the  others  are  hydroxy  or  ketone  derivatives. 

Skatole,  Tryptophane 

Skatole. — We  have  mentioned  the  fact  that  indole  is  important 
physiologically.  Associated  with  indole  in  this  relationship  is  the 
beta-methyl  homologue  of  indole  known  as  skatole.  Skatole  is  the 
substance  to  which  the  characteristic  odor  of  fasces  is  due.  Both  of 
these  compounds  are  present  in  faeces  and  are  the  result  of  putrefactive 
decomposition  of  protein. 

Tryptophane. — As  an  intermediate  product  in  the  decomposition 
of  proteins  we  have  the  amino  acid  known  as  tryptophane  which  may  be 
obtained  by  the  acid  hydrolysis  of  most  proteins  (p.  389).     Trypto- 
phane may  be  considered  either  as  an  indole  or  skatole  derivative. 
H 
C 

C— CH3 
CH 


C— CH2— CH(NH2)— COOH 


H 


Tryptophane 
Skatole  amino 

acetic  acid 
0-Indole  a-amino  propionic  acid 


INDIGO 


On  further  decomposition  tryptophane  yields  either  indole  or  skatole. 
Not  only  are  these  final  protein  decomposition  products  present  in  the 
fasces,  but  they  become  absorbed  from  the  intestine  and  pass  into  the 
urine  where  they  are  present  as  normal  constituents,  having  first  un- 
dergone oxidation  forming  indoxyl  and  skatoxyl  which  then  esterify 
with  sulphuric  acid  yielding,  in  the  case  of  indole,  indoxyl  sulphuric 
acid,  the  potassium  salt  of  which  has  been  wrongly  termed  indican. 

H 
C 

--  C—  OS02OK 


C  N 

H  H 

Potassium 
indoxyl  sulphate 

Skatol  probably  does  not  yield  the  corresponding  sulphuric  acid 
salt  but  is  present  in  urine  as  the  mono-carboxylic  acid  or  as  skatole 
acetic  acid. 

Indigo 

What  now  is  indigo  and  what  is  its  relation  to  these  "compounds  of 
the  indole  group?  Indigo,  which  is  sometimes  called  the  king  of  dyes, 
is  the  most  common  and  most  valuable  blue  dye.  It  was  originally 
obtained  solely  from  the  indigo  plant  and  has  been  known  for  a  long 
time.  The  chemical  study  of  this  natural  dye,  in  order  to  determine 
its  constitution  and  thus  make  possible  its  synthetic  preparation,  forms 
one  of  the  most  interesting  and  striking  examples  of  the  triumph  of 
modern  synthetic  organic  chemistry.  Without  attempting  to  discuss 
the  subject  in  its  historical  development  we  shall  show  the  final  results 
of  the  study  and  its  industrial  application. 

Aniline.  —  When  indigo  is  distilled  aniline  is  obtained,  a  fact  which 
gave  the  name  aniline  to  the  product  and  which  we  referred  to  in  dis- 
cussing that  compound  (p.  539). 

Anthranilic  Acid.  —  Also  from  indigo  we  may  obtain  anthranilic  acid 

,COOH  (i) 
which  is  ortho-ammo  benzoic  acid,  C6H4\ 

XNH2      (2) 


872  ORGANIC   CHEMISTRY 

Isatin,  Indole,  etc. — By  oxidation  indigo  yields  isatin  which  by  suc- 
cessive reductions  as  recently  explained  yields  di-oxindole,  oxindole 
and  finally  indole.  Also  indoxyl,  the  isomer  of  oxindole,  yields  indigo 
by  oxidation.  The  composition  formulas  of  indigo  and  these  last  com- 
pounds are  as  follows: 

C8H7N  Indole 

C8H7ON  Indoxyl  and  Oxindole 

C8H7O2N  Di-oxindole 

C8H5O2N  Isatin 

Ci6HioO2N2  Indigo 

These  facts  alone  indicate  that  indigo  probably  contains  two  indole 
groups  or  residues. 

Isatin  Chloride.— Now  isatin  which  is  a  di-ketone  of  di-hydro  in- 
dole, or  the  tautomeric  form,  a  mixed  ketone  and  hydroxyl  derivative 
of  indole,  yields  a  chloride  when  treated  with  phosphorus  pentachloride. 


,C--CO        +PC15    HCr         >C- 
HCl 


H 

Isatin  chloride 

On  treatment  of  isatin  chloride  with  zinc  dust  and  acetic  acid  the  chlo- 
rine is  eliminated  and  two  hydrogens  added  with  the  formation  of 
indigo.  The  reaction,  with  the  formula  for  indigo  which  is  supported, 
as  we  shall  find,  by  other  syntheses,  is  as  follows: 


H 
C 


CO  OC 


C       C— (Cl  +  H)     (H  4 
\f  H        H 

N  N  C 

H  H 

Isatin  chloride  1  Isatin  chloride 


INDIGO 


873 


or 


CH 


Indigo 


H 

C 

CO 

HC 

A 

c/\ 

HC 

"xx 

C 

\/ 

^s^ 

C 

\/ 

N 

H 

H 

Synthesis. — There  have  been  numerous  syntheses  of  indigo  some  of 
which  have  been  used  industrially  while  others  have  been  of  importance 
in  establishing  the  constitution  of  the  dye. 

From  Di-phenyl  Di-acetylene. — The  proof  that  the  two  isatin  or 
indole  residues  are  linked  together  by  the  carbons  is  in  the  synthesis 
of  indigo  from  di-phenyl  di-acetylene,  C6H5—  C  =  C— C  =  C— C6H5. 
This  compound  by  conversion  into  the  di-  (ortho-nitro)  product,  and 
treatment  with  sulphuric  acid  and  reduction  with  ammonium  sulphide, 
yields  indigo.  This  indicates  that  the  chain  of  carbon  linkings  remains 
as  in  the  above  compound. 


Di-o-nitro  di-phenyl  di-acetylene 


H2SCX 


874 


ORGANIC   CHEMISTRY 


Indigo 


Baeyer  and  Emmerling,  Indole  from  ortho-Nitro  Cinnamic  Acid. — 

The  first  relationship  between  members  of  the  indole  group  and  simpler 
benzene  derivatives  was  that  established  by  Baeyer  and  Emmerling, 
1869,  in  synthesizing  indole  from  ortho-miio  cinnamic  acid  by  fusion 
with  potassium  hydroxide  and  iron  filings.  The  steps  in  the  synthesis 
are  probably  as  follows: 


H 


CH=CH— COOH 


(+H) 


H  02 

o-Nitro  cinnamic  acid 


INDIGO 


875 


CH=CH— COOH 


(-CO,) 


C              N 
H            H2 
H 
C              CH  =  CH2 

Hcr^v  .  (+o)  HC 

HCl^^Jc^                                  HC 

C              N 

HTT 
-ll2 

H 
C 

OC  CH 
II 
C       CH 
\/ 

C           N 
H           H 

Indole 


Engler  and  Emmerling,  Indigo  from  ortho-Nitro  Acetophenone.— 
In  1870  Engler  and  Emmerling  first  synthesized  indigo  itself  by 
heating  ortho-nitro  acetophenone  with  lime  and  zinc  dust. 


H 
C 


CO—  CH3 


HC^N 
HCkJ 


\ 


C 

H 


N0 


o-Nitro  acetophe- 
none (2  mo/.) 


CH 


02N 


c=c 


Indigo 


876  ORGANIC    CHEMISTRY 

From  ortho-Nitro  Phenyl  Acetic  Acid.  —  Several  other  syntheses 
were  developed  by  Baeyer.  Starting  with  ortho-nitro  phenyl  acetic 

CH2—  COOH  (i) 
acid,  C6H4<f  ,  he  obtained  oxindole  by  the  reaction 

XN02  (2) 

already  given  (p.  866).     From  oxindole  by  oxidation  isatin  was  ob- 
tained and  this  through  the  chloride  yielded  indigo  (p.  872). 

Benzaldehyde,  ortho-Nitro  Cinnamic  Acid,  ortho-Nitro  Phenyl 
Propiolic  Acid.  —  Later  he  started  with  benzaldehyde  and  obtained  first 
benzal  chloride  which  by  condensation  with  sodium  acetate  yielded 
cinnamic  acid  salt. 

H  H 

C  C 


L  JcH  HcL  J 


C  C 

H  H 

Benzaldehyde  Benzal  chloride 


+  H2)CH—  COONa 
cH 


H 
C 

^CH^CH— COONa 
HC' 


H 

Cinnamic  acid 
(salt) 


From  the  cinnamic  acid  salt  by  nitration  he  obtained  ortho- 
nitro  cinnamic  acid.  This  yielded  a  di-bromide  which  by  loss  of 
two  molecules  of  hydrogen  bromide  was  converted  into  ortho-nitro 
phenyl  propiolic  acid  (p.  700). 


INDIGO 


877 


H 

C  CH  =  CH— COOH 

c/ 


HCf^N 

Hck/-k 

C  NO. 

H 

o-Nitro  cinnamic  acid 


2Br 


CHBr— CHBr— COOH 


(-2HBr) 


C=C— COOH 


propiolic  acid 

Finally  ortho-nitro  phenyl  propiolic  acid  when  heated  with  alkali  and 
glucose,  the  latter  acting  as  a  reducing  agent,  yielded  indigo.  He 
also  converted  ortho-nitro  phenyl  propiolic  acid  into  indigo  by  the 
following  series  of  reactions. 

H  H 

C  C=C— COOH  C  C—CH 


(-CO,) 


HC 


N02 


N02 


o-Nitro  phenyl 
propiolic  acid 


H 

o-Nitro  phenyl 
acetylene 


ORGANIC    CHEMISTRY 


H 
C 


C 
H 


HCr 


H 


H 

£=£(JJ          JJ)( 

^=c         c 

(    * 

Cr^  ^CH 

cL           JcH 

NO2 

02N            C 

H 

o-Nitro  phenyl  acetylene 

(2  wo/.) 

H 

H 

C                    C=C—  C=C                    C 

O/                       v            -""^ 

s 

Y^ 

CH 

c 

J. 

,H>.                  X 

CH 

\ 

/    \x/ 

C             N02 

02N             C 

H 

H 

Di-o-nitro  di-phenyl 
di-acetylene 

re-arrangement 

to  di-isatogen 

and  reduction 

; 

(P.  873) 

H              0 

0              H 

C              C 

C              C 

"V.        /  \ 

> 

/^^~ 

^CH 

;c= 

•c 

.A  / 

\/^ 

^CH 

C              N 

N              C 

H              H 

H              H 

-2H) 


HC 

HO 


Indigo 

The  reaction  probably  proceeds  as  above,  by  the  loss  of  carbon  dioxide 
with  the  formation  of  ortho-nitro  phenyl  acetylene.  This  condenses 
with  itself  by  the  loss  of  two  hydrogens  yielding  di-ortho-nitro  di-phenyl 
di-acetylene  and  this,  by  the  reactions  previously  discussed  (p.  874), 
rearranges  to  di-isatogen  which  by  reduction  yields  indigo.  This 
synthesis,  though  at  first  used  "on  an  industrial  scale,  was  not  however  a 
commercial  success  as  the  yield  of  ortho-nitro  cinnamic  acid  was  too 
small  and  the  loss  in  the  final  stage  was  too  large. 


INDIGO 


879 


Baeyer  and  Drewsen,  ortho-Nitro  Benzaldehyde. — A  later  syn- 
thesis of  Baeyer  and  Drewsen  was  by  the  condensation  of  ortho- 
nitro  benzaldehyde  with  acetone  in  the  presence  of  sodium  hydroxide. 


H 
C 


C 
H 


CHO  +  CH3— CO— CH3 


SNO2 


o-Nitro  benzaldehyde 


Acetone 


CH(OH)— CH2— CO— CH3 


2  mol. 
(-2CH3COOH) 


(-H20) 


Indigo 


88o 


ORGANIC   CHEMISTRY 


The  commercial  value  of  this  synthesis  was  increased  when  it  was  found 
that  benzaldehyde  could  be  prepared  directly  from  toluene.  Like  the 
preceding  synthesis  of  Baeyer,  however,  it  has  proved  too  expensive 
for  a  general  industrial  process  though  it  is  still  used  in  some  cases. 

Heumann's  Synthesis,  Phenyl  Glycine  Ortho-carboxylic 
Acid. — The  synthesis  that  has  resulted  in  placing  synthetic  indigo  on 
the  market  is  that  of  Heumann  by  the  fusion  of  phenyl  glycine  ortho- 
carboxylic  acid  with  caustic  potash.  The  product  of  this  fusion  is 
indoxyl  which  by  atmospheric  oxygen  is  oxidized  to  indigo.  The  in- 
dustrial success  of  this  synthesis  was  achieved  only  when  the  prepa- 
ration of  the  phenyl  glycine  ortho-carboxylic  acid  from  a  cheap  source 
was  accomplished. 

Naphthalene  to  Anthranilic  Acid. — Such  a  cheap  source  was  found 
in  naphthalene  which  was  converted  into  anthranilic  acid,  ortho- 
amino  benzoic  acid,  and  this  by  treatment  with  chlor  acetic  acid 
yields  phenyl  glycine  ortho-carboxylic  acid.  The  complete  synthesis 
is  as  follows:  Naphthalene  is  oxidized  to  0r/^0-phthalic  acid  which  then 
yields  phthalic  anhydride.  This  with  ammonia,  as  ammonium  car- 
bonate, yields  phthalimide  or  phthalamidic  acid. 


,COOH 


O 


\CQ/ 

Phthalic  anhydride 


NH    or 


COOH 


Phthalamidic  acid 

Phthalamidic  acid  is  then  converted  into  anthranilic  acid  by  the  action 


INDIGO 


88 1 


of  sodium  hypochlorite  or  hypobromite  as  in  the  Hofmann  reaction 
(p.  148),  and  the  anthranilic  acid  with  chlor  acetic  acid  yields  phenyl 
glycine  0r//w-carboxylic  acid. 


COOH 


+  NaOCl 


COOH 


\ 


Phthalamidic  acid 


Anthranilic 

acid 

o-Amino 
benzoic  acid 


NH(H  +C1)CH2— COOH 


Chlor  acetic  acid 


COOH 


NH— CH2— COOH 


Phenyl  glycine 
o-carboxylic  acid 


The  anthranilic  acid  may  also  be  converted  into  phenyl  glycine  ortho- 
carboxylic  acid  by  the  action  of  formaldehyde  and  potassium  cyanide, 
yielding  first  cyano-methyl  anthranilic  acid  which  on  hydrolysis  is 
converted  into  the  phenyl  glycine  compound. 


COOH 


Anthranilic  acid 

,COOH 


CH20  +  KCN 


+  2H20 


NH— CH2— CN 


COOH 


NH— CH2— COOH 


Cyano-methyl 
anthranilic  acid 


Phenyl  glycine 
o-carboxylic  acid 


Finally  the  phenyl  glycine  ortho-carboxylic  acid  is  fused  with  sodium 
hydroxide  and  converted  into  indoxyl  which  by  atmospheric  oxidation 
yields  indigo. 


882 


ORGANIC    CHEMISTRY 


Phenyl  glycine 
o-carboxylic  acid 


Indigo 

In  the  reactions  above  the  products  are  given  in  the  form  of  the  free 
acids  though  in  fact  the  sodium  or  potassium  salts  are  usually  obtained. 
In  practice  the  free  acid  may  be  secured  by  acidifying  though  the  salts 
are  often  used. 

Industrial  Indigo. — These  syntheses  of  indigo  have  been  considered 
rather  thoroughly  because,  as  previously  mentioned,  the  whole  problem 
of  the  industrial  synthesis  of  this  natural  dye  is  one  of  the  triumphs  of 
synthetic  organic  chemistry  and  it  illustrates  in  a  striking  way  how  com- 
plete must  be  the  study  of  such  a  problem  in  order  that  success  may 
result.  It  also  shows  how  the  study  of  the  constitution  of  a  compound 
must  be  supplemented  by  a  search  for  a  particular  synthesis  involving 
a  cheap  commercial  material  as  the  starting  point.  The  magnitude 
of  the  task  may  be  grasped  by  the  consideration  of  a  few  facts.  The 
period  of  time  from  the  first  synthesis  of  indole  and  indigo  to  that  of 
the  full  establishment  of  the  constitution  of  indigo  was  about  ten 
years.  From  the  first  apparently  commercial  synthesis  of  indigo  by 
Baeyer,  until  Heumann's  better  synthesis,  another  ten  years  elapsed; 
and  the  improvement  of  Heumann's  process,  with  the  finding  of  a  cheap 
starting  point  and  the  commercial  struggle  to  make  the  process  an 


INDIGO 


industrial  success,  occupied  about  twenty  years  more.  Thus  from 
1869  until  1909  the  problem  of  synthetic  indigo  occupied  the  atten- 
tion of  some  of  the  world's  greatest  organic  chemists  and  required  the 
expenditure  of  large  sums  of  money  in  purchasing  patents  and  erecting 
manufacturing  plants.  The  first  patents  of  Baeyer  were  sold  for  some 
one  hundred  thousand  dollars  and  probably  as  much  was  paid  for  those 
of  Heumann.  The  first  plant  for  the  production  of  synthetic  indigo 
cost  over  two  million  dollars  and  the  capitalization  of  the  combined 
synthetic  indigo  companies  of  Germany  amounts  to  about  five  million 
dollars. 

In  1907  the  total  production  of  synthetic  indigo  was  about  80  per 
cent  of  the  world's  consumption.  The  price  of  the  synthetic  compound 
was  about  $1.50  a  pound  and  the  natural  about  $1.75. 

The  increase  in  the  production  of  the  synthetic  indigo  has  decreased 
the  cultivation  of  the  indigo  plant,  especially  in  India  where  the  land 
formerly  used  for  this  purpose  is  now  used  for  other  crops  such  as  rub- 
ber, turmeric,  hemp,  cotton,  etc. 

Natural  Indigo.  —  Indigo  is  obtained  naturally  from  the  indigo  plant, 
Indigofera  tinctoria,  which  is  cultivated  in  tropical  countries,  e.g., 
India,  Java,  and  China.  It  is  one  of  the  oldest  and  most  valuable 
dyes  having  been  used  in  Egypt  as  early  as  1600  B.C.  and  is  still  used 
more  universally  than  any  other  blue  dye.  It  occurs  in  the  plant  in 
the  form  of  a  glucoside  known  as  indican.  When  the  plants  are  ex- 
tracted with  warm  water  a  natural  ferment  present  in  the  plant  hydro- 
lyzes  the  glucoside  into  its  constituent  parts,  viz.,  glucose  and  the  leuco 
base  of  the  dye  or  indigo  white.  After  the  extraction  and  fermentation 
the  extract  is  aerated  when  the  leuco  base  is  oxidized  and  indigo  results. 
It  is  a  dark  blue  substance  easily  powdered  and  giving  a  coppery  luster 
when  rubbed.  It  sublimes  at  170°  to  a  red  vapor.  It  is  insoluble  in 
water,  alcohol,  ether,  acid  or  alkali,  dissolving  slighty  in  hot  amyl 
alcohol,  chloroform,  carbon  di-sulphide,  etc.  Concentrated  sulphuric 
acid  forms  a  mono-sulphonic  acid  which  is  soluble  in  water  but  insoluble 
in  salt  solution.  Fuming  sulphuric  acid  forms  a  di-sulphonic  acid 
known  as  indigo  carmine.  Technically  indigo  is  classed  as  a  vat  dye. 
It  dyes  both  animal  and  vegetable  fibers  without  a  mordant.  An 
explanation  of  the  name  vat  dyes  will  be  found  in  special  books 
on  dyes. 


884  ORGANIC   CHEMISTRY 

D.  ALKALOIDS 

The  group  of  compounds  known  as  alkaloids  includes  substances 
usually  characterized  by  marked  physiological  activity.  They  occur 
most  commonly  in  plants  though  some  are  found  in  animals.  In  their 
chemical  character  they  are  complex  organic  nitrogen  bases  generally 
insoluble  in  water  but  yielding  salts  which  are  usually  soluble.  Some 
authors  classify  as  alkaloids  all  organic  nitrogen  bases  which  occur  in 
plants.  The  basic  character  of  the  compounds  is  indicated  in  their 
names  by  the  termination  ine.  While  it  is  difficult  to  define  or  classify 
the  alkaloids  with  exactness  the  characters  just  given  may  be  considered 
as  the  essential  ones.  The  best  idea  of  the  group  may  be  gained  by 
considering  a  brief  list  of  those  which  we  shall  discuss.  They  are  as 
follows:  conine,  piperine,  nicotine,  quinine,  cinchonine,  strychnine, 
brucine,  morphine,  codeine,  hyoscyamine,  atropine,  tropine,  cocaine, 
stovaine,  novocaine,  caffeine,  theobromine,  xanthine,  guanine  and 
adenine. 

In  this  list  there  will  be  recognized,  at  once,  several  substances  which 
have  long  been  known  and  used  in  medicine  because  of  their  physiolog- 
ical and  therapeutic  properties.  Several  of  them,  also,  are  generally 
considered  as  deadly  poisons  because,  in  overdoses,  the  effect  upon  human 
beings  is  fatal.  The  physiological  action  on  the  animal  body  is  of  dif- 
ferent types.  In  some  cases  partial  or  complete  insensibility  of  the 
nervous  system  is  produced.  Those  which  act  in  this  way  include  the 
narcotics  such  as  morphine.  In  other  cases  a  stimulation  of  the 
nerves  or  of  the  heart  results  as  with  atropine,  strychnine,  etc.  Some 
act  in  a  milder  way  and  cause  a  lowering  of  the  body  temperature. 
These  include  the  anii-pyretics  or  febrifuges  such  as  quinine. 

The  reason  for  considering  these  compounds  in  this  the  last  chapter 
of  the  book  is  not  because  they  are  more  complex  or  less  known  than 
some  other  groups  but  because  in  their  chemical  classification  most  of 
those  we  shall  study  are  related  to  the  two  hetero-cyclic  compounds 
recently  discussed,  viz.,  pyridine  and  quinoline. 

It  should  be  stated  that  the  treatment  which  follows  is  in  no  sense 
exhaustive  either  as  to  the  properties,  etc.,  of  the  alkaloids  referred  to, 
or  as  to  the  methods  and  reactions  by  which  the  constitution,  when 
known,  has  been  established.  All  that  is  attempted  here  is  a  brief 
presentation  of  the  more  common  and  important  members,  their  origin 
and  properties  and  their  constitution  as  related  to  compounds  we  have 
previously  studied. 


ALKALOIDS 


88S 


ALKALOIDS  RELATED  TO  PYRIDINE 
Conine 

The  first  alkaloid  which  we  shall  consider  is  of  especial  interest 
historically.  The  Greek  philosopher  Socrates  was  put  to  death  by 
being  compelled  to  drink  an  extract  of  hemlock,  Conium  maculatum. 
In  the  fruit  and  leaves  of  this  plant  there  are  present  six  different  alka- 
loids one  of  which  is  named  from  the  plant  and  is  known  as  conine. 
This  compound  is  a  colorless,  strongly  alkaline  liquid  acting  as  a  deadly 
poison  when  taken  in  more  than  extremely  small  doses.  Physiologically 
it  produces  paralysis  of  the  motor  nerve  terminations  and  depression 
of  the  central  nervous  system. 

Conine  is  also  of  especial  interest  because  it  is  the  first  natural  alka- 
loid to  have  been  made  synthetically.  In  1886  Ladenburg  prepared  it 
from  a//>/fa-picoline  which  is  alpha-meihyl  pyridine.  By  condensing  this 
with  acetaldehyde  he  obtained  alpha-aHyl  pyridine  and  by  reduction 
this  yielded  the  corresponding  saturated  compound,  viz.,  alpha-propyl 
piperidine.  This  proved  to  be  inactive  conine  and  from  it  the  dextro 
and  levo  isomers  were  obtained.  The  dextro  conine  thus  prepared 
is  identical  with  the  natural  alkaloid  of  hemlock.  The  reactions  are  as 
follows: 


H 
C 


:O 


CH 


C— CH(H2 


0)CH— CH3 


N 


a-Methyl  pyridine 
a-Picoline 

H 
C 


HC 
H 


o 

N 

a-Allyl  pyridine 


c-CH  =  CH-CH3 


886  ORGANIC    CHEMISTRY 

Piperine 

The  fruit  of  the  plant  Piper  nigrum  is  the  common  black  pepper  of 
the  household.  This  fruit  yields  an  alkaloid  known  as  piperine  present 
to  about  4  to  9  per  cent  in  commercial  pepper.  On  hydrolysis  the 
alkaloid  yields  piperidine  or  hexa-hydro  pyridine  and  an  acid  known  as 
piperic  acid.  Piperine  is  thus  considered  as  a  piperidine  amide  of 
piperic  acid.  Physiologically  this  alkaloid  acts  like  quinine  but  is 
less  active  and  is  uncertain.  It  is  only  rarely  used  in  medicine. 

Nicotine 

The  alkaloid  nicotine  is  present  in  tobacco,  Nicotiana  tabacum. 
In  discussing  the  derivatives  of  pyridine  it  was  stated  (p.  858)  that  the 
fofo-mono-carboxy  acid  of  pyridine  is  known  as  nicotinic  acid  and  that  it 
is  obtained  by  the  oxidation  of  the  alkaloid  nicotine.  Therefore  the 
alkaloid  undoubtedly  contains  the  pyridine  group.  It  has  been  synthe- 
sized by  Pictet  and  its  constitution  established  as  a  pyridine  deriva- 
tive of  methyl  pyrrolidine.  This  constitution  was  first  suggested  by 
Pinner. 

H2C  —  CH2 


HC      CH2  N-methyl 

\    /  pyrrolidine 

N  Nicotine 


CH3 

Natural  nicotine  is  the  levo  variety.  Physiologically  the  alkaloid 
affects  both  the  central  and  peripheral  nerves  and  increases  the  activity 
of  the  secreting  glands.  In  more  than  minimum  doses  it  is  a  poison. 
It  is  not  used  to  any  extent  in  medicine  though  recently  it  has  been 
suggested  as  a  hypodermic  in  cases  of  tetanus.  The  salicylic  acid 
salt  is  also  used  somewhat  for  skin  diseases.  Tobacco  extracts  and 
also  powdered  tobacco  are  used  as  insecticides,  their  value  depending 
upon  the  amount  of  nicotine  present. 

ALKALOIDS  RELATED  TO  QUINOLINE 

The  alkaloids  related  to  quinoline  include  three  which  are  frequently 
used  in  medicine  and  on  that  account  are  commonly  known.     These 


ALKALOIDS  gg~ 

three  are  the  almost  universal  febrifuge,  quinine,  the  stimulant  or  tonic 
strychnine  and  the  narcotic,  morphine.  The  first  two  are  related  to 
quinoline  and  the  last  to  iso-quinoline. 

Quinine  and  Cinchonine 

The  bark  of  the  cinchona  tree,  Cinchona  o/icinalis,  yields  several 
alkaloids.  The  most  important  of  these  cinchona  alkaloids  is  quinine, 
C2oH24O2N2.  Associated  with  it  is  cinchonine,  Ci9H22ON2,  and  two 
which  are  stereo-isomers  of  these,  viz.,  quinidine  and  cinchonidine. 

The  relation  of  quinine  and  cinchonine  to  quinoline  is  shown  by 
their  oxidation  products.  As  mentioned  in  connection  with  quinoline 
the  alkaloid  cinchonine  when  oxidized  yields  a  mono-carboxy  quinoline 
known  as  cinchoninic  acid.  Similarly  quinine  yields  quininic  acid 
which  is  a  meth-oxy  derivative  of  cinchoninic  acid. 

COOH 


r.     .  oxidation       [I!     Cinchoninic  acid 

Cinchonine  Quinoline  mono- 

carboxylic  acid 


COOH 


~    .   .          oxidation 

Quinine >  Quunmc  acid 


These  reactions  indicate  that  these  two  alkaloids  each  contain  a  quino- 
line group.  In  addition  to  these  two  derivatives  of  quinoline,  each  of 
the  alkaloids  yields  another  acid,  which  is  the  same  in  both  cases.  It  is 
known  as  loiponic  acid.  These  facts  indicate  that  quinine  is  a  meth-oxy 
derivative  of  cinchonine  and  that  each  alkaloid  consists  of  two  parts, 
one  a  quinoline  group  and  the  other  a  complex,  CioHi6ON,  or  CioHu- 
(OH)N.  Although  neither  of  the  alkaloids  has  yet  been  synthesized 
the  probable  constitution  of  the  second  half  has  been  suggested  by 
Konig  and  the  accepted  constitution  is  as  follows: 


888  ORGANIC   CHEMISTRY 


H 
C 


H2CCH2CH—  CH  =  CH2 

I  | 

CHOH—  HC  CH2  CH2 


N 

Cinchonine 


H 
C 


CH3O— C 


H2CCH2CH— CH=CH2 

I  I 

CHOH— HC  CH2  CH2 


Quininje 


The  other  two  cinchona  alkaloids,  cinchonidine  and  quinidine,  are 
stereo-isomers  of  cinchonine  and  quinine. 

The  cinchona  tree,  from  the  bark  of  which  these  alkaloids  are 
obtained,  was  originally  found  only  on  the  eastern  slope  of  the  Andes  in 
South  America.  The  cultivation  of  this  species,  and  other  species  of 
the  same  genus,  was  introduced  into  Java,  India,  Ceylon,  Jamaica 
and  Australia.  At  present  the  production  of  bark  in  Java  is  greater 
than  in  any  other  country.  As  early  as  1639  the  cinchona  bark  was 
introduced  into  Europe  but  it  was  not  until  1792  that  an  impure  alka- 
loid was  isolated  and  a  little  later  given  the  name  quina.  In  1820  this 
impure  alkaloid  was  separated  into  two  compounds  named  quinine 
and  cinchonine.  The  bark  contains  about  3  per  cent  quinine  combined 
with  acids,  tannic  and  quinic,  from  which  it  is  set  free  by  the  action 
of  lime.  The  free  base  is  then  extracted  with  petroleum  ether  or 


ALKALOIDS 

chloroform.  It  is  a  di-(tertiary  nitrogen)  base  forming  salts,  sulphates 
and  chlorides,  in  which  form  it  may  be  recrystallized  and  separated 
from  the  other  alkaloids  present.  The  free  base  forms  a  crystalline 
hydrate  melting  at  57°,  the  anhydrous  base  melting  at  173°-! 75°. 
The  base  is  sparingly  soluble  in  hot  water  but  readily  in  chloroform, 
alcohol  and  ether.  The  natural  alkaloid  is  levo  rotatory.  The  free 
base  forms  both  acid  and  neutral  salts.  The  neutral  sulphate  crystal- 
lizes with  7H2O  and  is  the  common  commercial  form  in  which  the  alka- 
loid is  used.  It  is  sparingly  soluble  in  water. 

The  physiological  action  of  the  cinchona  alkaloids  is  that  of  an 
antipyretic  or  febrifuge,  lowering  the  body  temperature  in  case  of  fevers. 
Quinine  retards  the  action  of  oxidase  enzymes  and  acts  as  a  poison  to 
certain  organisms,  especially  that  of  malaria.  Its  first  use  was  as  a 
specific  for  this  form  of  fever.  It  has  a  very  bitter  taste  and  in  common 
with  other  substances  of  like  properties  it  acts  on  the  alimentary 
canal  causing  increased  secretion  of  digestive  juices. 

Strychnine  and  Brucine 

The  two  alkaloids  strychnine,  C2iH2202N2,  and  brucine,  C23H26- 
64 N2,  occur  together  in  the  seeds  of  nux-vomica,  Strychnos  nux-wmica, 
found  in  India,  and  in  the  Ignatius  bean,  Strychnos  Ignatii,  found  in  the 
Philippine  Islands.  The  seeds  yield  from  3-5  per  cent  of  total  alka- 
loids. The  alkaloids  are  extracted  from  the  seeds  in  practically  the 
same  way  as  quinine  from  cinchona  bark.  Both  of  the  free  bases  are 
crystalline  and  slightly  soluble  in  water.  They  are  both  mono-acid 
bases  forming  soluble  sulphates,  nitrates  and  chlorides.  Strychnine 
is  not  colored  by  sulphuric  acid  but  when  moistened  with  the  acid,  in 
the  presence  of  a  crystal  of  potassium  bi-chromate,  a  series  of  color 
changes  is  produced  beginning  with  blue,  then  violet,  red  and  finally 
yellow.  Brucine  by  similar  treatment  gives  no  color  changes  but  with 
nitric  acid  gives  a  red  color  that  changes  to  violet  when  a  little  stannous 
chloride  is  added. 

Both  of  these  alkaloids  contain  a  quinoline  group  but  the  constitu- 
tion as  developed  by  a  study  of  their  reactions  and  products  of  oxida- 
tion is  more  complex  than  is  desirable  to  discuss  here.  The  relation 
of  the  two  has  been  shown  to  be  that  brucine  is  a  di-meth-oxy  derivative 
of  strychnine  which  agrees  with  the  composition  formulas  as  given. 

Physiologically  the  two  are  similar  though  brucine  is  much  less 


8go 


ORGANIC   CHEMISTRY 


toxic.  Strychnine  is  very  poisonous  and  acts  principally  on  the  spinal 
cord  causing  convulsions  and  stopping  of  respiration.  In  small  doses, 
as  used  medicinally,  strychnine  retards  the  heart  action  and  increases 
blood  pressure.  It  is  chiefly  used  as  a  tonic  for  local  action  on  the 
digestive  organs  and  has  also  been  used  for  chronic  alcoholism.  The 
alkaloids  are  used  in  the  form  of  their  soluble  salts  or  in  that  of  extract 
or  tincture  of  nux-wmica. 

Morphine,  Codeine,  Narcotine,  Papaverine 

The  substance  known  as  opium  yields  two  very  important  narcotic 
alkaloids,  viz.,  morphine,  Ci7Hi9O3N,  and  codeine,  Ci8H2iO3N.  With 
these,  several  other  alkaloids  are  also  present,  only  two  of  which  will 
be  mentioned,  viz.,  narcotine  and  papaverine.  These  opium  alkaloids 
are  related  not  to  quinoline  but  to  iso-quinoline  (p.  865)  as  is  proven  by 
their  decomposition  products.  Codeine  has  been  proven  to  be  the 
meth-oxy  derivative  of  morphine  the  two  being  related  as  are  quinine 
and  cinchonine.  Morphine  proves  to  be  a  di-hydroxyl  compound 
with  a  third  oxygen  probably  analogous  to  the  oxygen  in  furfuran. 
Furthermore,  it  has  been  shown  that  the  larger  part  of  the  molecule 
does  not  contain  the  nitrogen  and  is  in  the  form  of  a  phenanthrene 
(p.  807)  grouping.  All  of  the  evidence  indicates  that  morphine  and 
codeine  are  derivatives  of  3-4-6  tri-hydroxy  phenanthrene.  With  one 
of  the  benzene  rings  of  the  phenanthrene  nucleus,  a  pyridine  ring  is 
linked,  as  in  isoquinoline.  The  constitution  generally  accepted  is 
that  suggested  by  Pschorr  and  modified  by  Knorr. 
CH 


HOC 


CH 


N— CH< 


HOHC 


C      H      CH2 
H2 

(Pschorr) 


Morphine 


8gi 


Morphine 

C 

H2 

N— CH3 

(Knorr) 

Cobeine  is  the  methyl-phenyl  ether  with  the  hydroxyl  hydrogen  in 
position  3  replaced  by  methyl.  Both  morphine  and  codeine  are  crystal- 
line compounds  reacting  as  tertiary  mono-acid  bases.  Morphine  is 
slightly  soluble  in  water,  codeine  being  more  so,  the  former  being  more 
bitter  in  taste  than  the  latter.  The  salts  are  soluble  and  in  this  form 
the  alkaloids  are  used  in  medicine  though  codeine  is  also  used  as  the 
free  base. 

Opium. — This  well-known  substance  from  which  morphine  and 
codeine  are  obtained  is  the  dried  latex  (juice)  of  the  unripe  fruit  of  the 
opium  poppy,  Papaver  somniferum.  The  use  of  opium  as  a  narcotic 
has  been  practised  from  early  times  and  the  poppy  plant  has  been 
cultivated  on  a  large  scale  in  India,  China,  Persia  and  Asia  Minor 
(Smyrna).  The  opium  used  in  medicine  is  largely  obtained  from 
Smyrna.  The  recent  exclusion  of  India  grown  opium  from  China  for 
opium  smoking  and  the  prohibition  of  its  growth  in  China  has  greatly 
affected  the  production.  The  number  of  different  alkaloids  obtained 
from  opium  is  very  large,  larger  than  from  any  other  one  plant. 
Twenty-five  different  alkaloids  have  been  isolated,  the  four  principal 
ones  being  those  mentioned.  The  percentage  amounts  of  these  four 
in  Smyrna  opium  is  as  follows: 

Morphine     9 . 00-10 .  oo  per  cent 

Narcotine     5.00  per  cent 

Papaverine  0.8  per  cent 

Codeine       o .  3-0  4        per  cen  t 


892  ORGANIC    CHEMISTRY 

Morphine  was  first  isolated  as  a  pure  substance  about  1814  and  its 
composition  determined  in  1831.  The  isolation  of  morphine  and  co- 
deine is  similar  to  that  of  quinine,  by  extracting  the  opium  with  warm 
water  and  then  treating  the  extract  with  lime.  The  two  are  then 
separated  by  the  different  solubility  of  the  free  bases. 

Physiological  Action. — The  opium  alkaloids  are  narcotics  in  their 
physiological  action.  Morphine  is  exceedingly  poisonous,  the  others 
less  so.  Their  action  is  on  the  central  nervous  system  on  which  they 
exert  both  a  depressing  and  exciting  influence.  Codeine  is  less  depress- 
ing than  morphine.  Morphine  is  fatal  to  man  in  amounts  of  0.2-0.3 
gram.  Continued  use  of  the  drug  for  producing  sleep  results  in  toler- 
ance of  the  body  for  it  and  much  larger  doses  are  required  to  produce 
the  usual  result. 

Heroine. — Two  derivatives  of  morphine,  used  as  synthetic  narcotics 
or  hypnotics,  deserve  attention.  The  first  of  these  is  known  as  heroine. 
It  is  the  di-acetyl  morphine.  It  resembles  morphine  in  its  action  but 
does  not  produce  as  great  mental  depression.  The  second  synthetic 
drug  is  the  ethyl  phenyl  ether  corresponding  to  codeine.  It  is  known 
as  dionine.  It  resembles  codeine  in  its  action.  The  benzyl  phenyl 
ether  is  known  as  peronine. 

DI-HETERO-CYCLIC  ALKALOIDS 
Hyoscyamine,  Atropine,  Tropine 

The  alkaloids  of  the  next  group  have  the  constitution  of  di-hetero- 
cyclic  compounds.  The  first  three  to  be  considered  are  hyoscyamine, 
C17H23O3N;  atropine,  Ci7H23O3N;  and  tropine,  CgHisON.  Because 
of  their  source  they  are  termed  Solanacea  alkaloids,  being  present  in 
plants  belonging  to  the  botanical  family  of  this  name.  To  this  same 
family  belong  the  common  edible  potato  and  the  poisonous  plant  known 
as  deadly  night-shade,  Atropa  belladona.  Of  these  three  alkaloids 
hyoscyamine  only  occurs  as  a  natural  alkaloid  in  the  plants.  The 
other  two  are  obtained  from  it,  atropine  being  a  stereo-isomer  and 
tropine  a  product  of  hydrolysis.  When  either  hyoscyamine  or  atro- 
pine is  hydrolyzed  two  products  are  obtained,  one  a  nitrogen  base  known 
as  tropine,  the  other  an  acid,  tropic  acid. 

C17H2303N  +  H20        >        CsH^ON  +  C9H1oO3 

Hyoscyamine  Tropine  Tropic 

or  acid 

Atropine 


ALKALOIDS 

Hyoscyamine  and  atropine  are  therefore  tropic  acid  esters  of  the  base 
tropine.  The  constitution  of  tropine  according  to  Willstater  is  as 
follows: 

H2C-       -CH-       -CH, 

I  I 

N— CH3       CHOH        Tropine 

H2C-       -CH-       -CH2 

This  represents  a  di-hetero-cyclic  compound  made  up  of  two  conju- 
gated rings  with  three  members  common.  One  of  the  rings  is  a  hydro- 
genated  pyridine,  the  other  a  hydrogenated  pyrrole.  As  tropine  is  ob- 
tained by  hydrolyzing  either  atropine  or  hyoscyamine  both  of  these 
must  therefore  contain  this  same  grouping.  The  formula  assigned  to 
them  is  as  follows,  atropine  being  the  inactive  variety  and  hyoscyamine 
the  lew  form. 

H2C-  -CH-  -CH2 

I  ,CH2OH  Hyoscyamine 

N— CH3  CHOOC— CH<^  (leva) 

I  C6H5  Atropine  (in.) 

H2C-  -CH-  -CH2 

Hyoscyamine  is  found  in  Atropa  belladonna  (night-shade)  and  in 
several  species  of  Hyoscyamus  from  which  its  name  is  derived.  It  is 
a  crystalline  compound,  m.  p. 108.5°,  somewhat  soluble  in  water  but  more 
readily  in  chloroform,  alcohol  or  benzene.  It  is  levo  rotatory  and 
yields  crystalline  salts  more  soluble  in  water  than  the  base  itself. 
With  acids  or  alkalies  hyoscyamine  hydrolyzes  as  previously  stated 
yielding  tropine  and  tropic  acid. 

Atropine  does  not  occur  as  such  in  the  solanaceae  plants  but  is 
formed  from  the  hyoscyamine  present  by  treatment  with  dilute  alka- 
lies, when  isomerization  takes  place  and  the  inactive  form  of  the  alka- 
loid is  obtained.  It  is  crystalline,  m.p.  115.5°,  and  only  slightly  soluble 
in  water  but  soluble  in  alcohol  and  chloroform.  The  salts  are  crystal- 
line and  soluble  in  water. 

Tropine  is  a  simpler  base  than  the  other  alkaloids  and  is  not  found 
as  such  in  the  plants  but  is  obtained  by  hydrolyzing  not  only  atropine 
and  hyoscyamine  but  other  solanaceae  alkaloids  as  well.  It  is  crys- 
talline, m.p.  63°,  and  is  soluble  in  water,  alcohol,  ether  or  benzene. 
As  shown  in  its  formula  it  is  an  alcohol  yielding  esters  with  tropic  acid, 


8Q4  ORGANIC    CHEMISTRY 

viz.,  atropine  and  hyoscyamine.     Other  esters  with  organic  acids  have 
been  prepared  and  used  in  medicine. 

In  their  physiological  action  atropine  and  hyoscyamine  are  similar 
and  exert  what  is  termed  a  mydriatic  action  causing  dilation  of  the  pupil 
of  the  eye.  This  action  may  be  produced  eithef  by  external  applica- 
tion or  by  taking  internally.  As  little  as  i  part  atropine  in  130,000 
parts  of  water  will  exert  a  distinct  action  on  the  eye.  They  decrease 
body  secretions  and  also  affect  the  heart.  Taken  internally  they  are 
poisonous  in  as  little  as  o.i  gm.  Tropine  exerts  no  mydriatic  action 
when  applied  to  the  eye  but  in  large  doses  internally  it  does  produce 
dilation.  In  addition  to  the  use  of  these  alkaloids  in  the  pure  form, 
extracts  of  belladonna  are  also  used. 

Cocaine 

Belonging  to  the  same  chemical  group  as  atropine  is  the  important 
alkaloid  cocaine,  CnH^iC^N.  It  is  obtained  from  the  leaves  of  the 
coca  plant,  Erythroxylon  coca,  which  grows  in  South  America  (Bolivia 
and  Peru)  and  in  Java  and  Ceylon.  Distinction  should  be  made  be- 
tween the  coca  plant  and  the  cacao  bean  from  which  cocoa  and  chocolate 
are  made. 

Cocaine  like  atropine  and  hyoscyamine  hydrolyzes  into  a  simpler 
nitrogen  base  and  other  products.  The  base  is  known  as  ecgonine 
and  the  other  products  obtained  are  methyl  alcohol  and  benzoic  acid. 
The  hydrolysis  proceeds  in  two  steps  as  follows: 


C17H2104N        _  CH3—  OH  +  Ci6H1904N 

Cocaine  Methyl  J  Benzoyl 

alcohol  ecgonine 

C9Hi503N  +  C6H5—  COOH 

Ecgonine  Benzoic  acid 

This  hydrolysis  indicates  that  the  simpler  base  ecgonine  is  both  an 
alcohol  and  an  acid  and  that  cocaine  is  the  double  ester  of  this  base 
with  benzoic  acid  and  methyl  alcohol.  Ecgonine  bears  the  same  rela- 
tion to  cocaine  that  tropine  does  to  atropine.  In  its  reaction  ecgo- 
nine proves  to  be  very  similar  to  tropine  and  as  indicated  by  its 
composition  formula  it  differs  simply  by  CC>2. 


C8Hi5ON 

Ecgonine  Tropine 

This  indicates  that  ecgonine  is  the  mono-carboxyl  derivative  of  tropine 
and  according  to  Willstater's  formula  for  tropine  ecgonine  is  as  follows: 


SYNTHETIC  ANESTHETICS  895 

H2C-  — CH-  -CH— COOH 


N— CH3  CH— OH  Ecgonine 


H2C CH-  — CH2 

As  cocaine  by  its  hydrolysis  proves  to  be  a  methyl  and  benzoyl  deriva- 
tive of  ecgonine  its  constitution  is  represented  by  the  following  formula: 

H2C-        CH-  -CH— COOCH3 

I  I 

N-CH3  CH— OOC— C6H5  Cocaine 

H2C-  -CH-  -CH2 

Ecgonine  like  tropine  does  not  occur  as  such  in  plants.  The  partially 
hydrolyzed  cocaine,  viz.,  the  benzoyl  ecgonine,  is  a  natural  plant  alka- 
loid. An  ester  analogous  to  cocaine  with  the  radical  of  cinnamic 
acid,  C6H5— CH  =  CH— COOH,  in  place  of  that  of  benzoic  acid,  is  a 
natural  alkaloid  in  Java  coca  leaves  and  is  known  as  cinnamyl  cocaine. 

It  was  known  for  some  time  that  the  natives  of  Bolivia  and  Peru 
chewed  coca  leaves  with  lime  as  a  stimulant.  The  action  is  due  to  the 
alkaloids  present  in  the  leaves  of  which  cocaine  is  the  most  important. 
At  present  both  the  coca  leaves  and  the  crude  extract  of  cocaine  are 
articles  of  commerce  from  those  countries  where  the  coca  plant  grows. 
The  alkaloid  is  extracted  with  sodium  carbonate  and  petroleum  ether. 
It  is  a  crystalline  compound,  m.p.  98°,  soluble  in  alcohol,  ether,  benzene 
or  petroleum  ether  and  slightly  soluble  in  water.  It  forms  well  crys- 
tallized soluble  salts,  the  hydrochloride  being  the  one  mostly  used. 

Physiologically,  cocaine  is  an  anesthetic  and  a  mydriatic  (dilates 
the  pupil  of  the  eye).  It  is  bitter  to  the  taste  and  very  poisonous. 
When  taken  internally  it  acts  on  the  central  nervous  system  causing 
paralysis  and  delusions.  The  importance  of  cocaine  in  medicine  is  as  a 
local  anesthetic,  and  though  used  originally  for  minor  operations  it 
is  now  administered  for  larger  ones.  The  anesthesia  produced  is  of 

short  duration. 

Synthetic  Anesthetics 

The  importance  of  cocaine  in  surgery  has  led  to  the  study  of  its 
chemical  constitution  and  to  the  preparation,  by  synthetic  methods, 
of  analogous  compounds  having  the  beneficial  anesthetic  properties 


896 


ORGANIC   CHEMISTRY 


but  free  from  the  highly  toxic  action  of  the  natural  alkaloid.  Atten- 
tion was  first  directed  to  the  preparation  of  compounds  very  similar  to 
cocaine. 

alpha-Cocaine.  —  One  of  these  is  isomeric  with  cocaine  and  is  known 
as  alpha-cocaine.  In  it  the  carboxyl  and  hydroxyl  are  both  linked  to 
the  same  carbon,  i.e.,  the  hydroxyl  is  alpha  to  the  carboxyl.  Though 
so  similar  to  cocaine  in  structure  and  resembling  it  in  general  properties 
it  does  not  produce  anesthesia. 

H2C 


H2C 


alpha  -Eucaine.  —  A  similar  compound  containing  the  same  pyridine 
ring  as  in  cocaine  and  also  with  the  above  alpha-hydroxy  relationship 
is  derived  from  tri-acetone  amine  and  is  known  as  alpha-eucame. 
Tri-acetone  amine  by  addition  of  hydrogen  cyanide  and  hydrolysis 
yields  the  alpha-hydroxy  acid.  Esterification  with  benzoic  acid  and 
methylation  with  methyl  alcohol  then  yields  alpha-eucame. 


^. 

: 

r 

*£], 

ST—  CH3 

^TT 

^ 
< 

,X12 

,COOCH3 
^OOCC6H5 

:n2 

L/JLX 

a-Cocaine 

CH3 

)> 
CH/ 


CO  +  NH3 


CH 
CH 
CH 
CH 


NH 


CH2 

CO  +  HCN 


Acetone  Ammonia 

(3  mo/.) 


3v 
)>C 


CH 


CH 


CH 


N— H       C<( 
I  |XOH 


Tri-acetone 
amine 

CH3 
| 
H3C—  C 


CH 


.COOCH, 


N—  CH3    C 


CH2 


X 


OOCC6H5 


H3C—  C 


CH 


CH3 

a-Eucaine 


SYNTHETIC  ANESTHETICS  897 

This  compound  possesses  anesthetic  properties  and  is  less  toxic 
than  cocaine.  It  is  irritating  when  injected  into  the  body  and  is  now 
replaced  by  beta-eucaine  which  is  a  similar  compound  derived  from 
acetaldehyde  di-acetone  amine,  vinyl  di-acetone  amine. 

beta-Eucaine.— The  di-acetone  amine  yields  an  alcohol  and  the 
benzoyl  ester  of  this,  in  the  form  of  the  hydrochloride  salt,  is 
beta-eucaine. 

•CH3 

H3C- 
CH3 

)>CO  +    NH3  -f  CHsCHO 
CH8 


Acetone  Ammonia        Acetaldehyde  Vinyl  di-acetone 

(2  mol.)  amine 

CH3 

H3C— C-        -CH2 

I  | 

NH.HC1    CHOOCC6H5 

H3C— C-        -CH2 
H 

/3-Eucaine 

This  compound  is  readily  soluble  in  water,  stable  at  100 
solution,  is  less  toxic  than  cocaine  or  alpka-eucaine  and  is  as  strongly 
anesthetic  as  cocaine  itself. 

Stovaine.  Alypine. — This  study  of  cocaine  and  eucaine  led  to  the 
examination  of  other  compounds  containing  an  alcohol-amine  ester 
grouping,  similar  to  that  present  in  these  anesthetics.  The  formula 
for  cocaine  contains  the  following  grouping: 

I  HoC  HC  -CH— COOCH3 

N-  |  | 

|       |      |  N— CH3    CH—OOC— C6H5 

-C— C— C— OOC— R 

H2C  -HC-          -CH, 

Cocaine 

57 


ORGANIC   CHEMISTRY 

Two  important  synthetic  products  containing  similar  alkamine  ester 
groupings  are  stovaine  and  alypine. 

CH3 

Cl\|  CH3  OOCC6H5 

H— N— CH3  CH3  or  \    / 

I  C 

/    \ 
-C-       OOCC6H5  C2H&  CH2-N(CH3)2HC1 

H  C2H5 

Stovaine 

C1H(CH3)2N— CH2  OOCC6H5 

\    / 
C 

/    \ 
C2H5  CH2— N(CH3)2HC1 

Alypine 

Both  stovaine  and  alypine  are  very  valuable  anesthetics  being  rapid 
in  their  action  and  similar  to  cocaine  without  its  injurious  effects  on  the 
heart  and  respiration.  They  are  used  chiefly  for  spinal  anesthesia. 
Orthoform. — Another  group  of  synthetic  anesthetics  are  derivatives 
of  para-amino  benzole  acid  or  of  amino  hydroxy  benzoic  acids.  Two 
of  these  are  known  as  orthoform  and  new  orthoform. 


-OH  S         >  -NH 


COOCH3  COOCH3 

'  Orthoform  New  Orthoform 

p-Amino  m-hydroxy  benzoic  m-Amine  p-hydroxy 

acid,  methyl  ester  benzoic  acid,  methyl  ester 

The  orthoforms  are  both  anesthetic  and  antiseptic  producing  anesthe- 
sia when  sprayed  or  dusted  upon  wounds. 

Anesthesine.  Novocaine. — Anesthesine,  another  member  of  this 
group,  is  simply  the  ethyl  ester  of  para-amino  benzoic  acid.  A  recent 
very  valuable  synthetic  anesthetic  is  related  to  anesthesine  and  also 
ta  cocaine.  It  is  known  as  novocaine  and  is  the  di -ethyl  amine  deriva- 
tive of  anesthesine. 


NIL 


SYNTHETIC    ANESTHETICS 
NH2 


COOC2H5 

Anesthesine 


COOCH2— CH2— N(C2H5)2HC1 

Novocaine 


In  novocaine  it  will  be  seen  that  there  is  present  the  same  alkamine 
ester  grouping  which  is  characteristic  of  cocaine.     The  compound  is 
prepared  by  the  following  reactions. 
CH2— OH  CH2— OH 

+  H)— Br       ->       |  +H)N(C2H5)2 


CH2— (OH 

Glycol 


CH2— (Br 

Glycol    brom 
hydrine 


CH2— OH 


C6H5— CH3 

Toluene 


,N02(p) 


CH2— N(C2H5)2 

Di -ethyl  a  mine  glycol 

/N02(p) 


C6H, 


p-Nitro  toluene 


XCOOH 

p-Nitro  benzoic 
acid 


,N02(p) 


,NH,(p) 


NH2(p) 


C6H 


X 


(p)-Amino 
benzoyl  chloride 


,NH2(p) 


C6H, 


p-Nitro  berizoyl 
chloride 


CO(C1        H)OCH2—  CH2—  N(C2H5) 


Di-ethyl  amine  glycol 


or 


NH, 


COOCH2— CH2— N(C2H5)-> 


XCOC1 

p-Amino  benzoyl 
chloride 


HC1 
COOCH2— CH2-N(C2H6)2 


Novocaine 


QOO  ORGANIC    CHEMISTRY 

PURINE  ALKALOIDS 

The  purine  group  of  alkaloids  includes  the  vegetable  alkaloids 
caffeine,  theobromine,  theophylline  and  the  animal  alkaloids  xanthine, 
hypoxanthine,  guanine  and  adenine.  The  most  common  substance 
which  is  a  purine  compound  is  uric  acid,  but,  though  directly  related 
to  the  alkaloids  given  above,  it  is  not  itself  usually  considered  as  an 
alkaloid.  The  constitution  of  uric  acid  has  been  fully  considered 
(Part  I,  p.  442).  It  is  the  tri-hydroxy  derivative  of  a  substance  known 
as  purine  which  is  the  mother  substance  of  the  purine  alkaloids  also. 

N*=  -CH 

a/             I  7 

HC  ,C NH 

^CH 

$  8 

N— C N 

Purine 

/=PS  NH-C  =  0 

HO— C  C NH  or 


N— C N 


0  =  C  C— NH, 

C— OH  \          ||  )c  =  0 

NH— C— NH' 


Uric  acid,     2-6-8-Tri-hydroxy  purine 

enol  form  keto  form 

As  shown  in  the  above  formulas  uric  acid  exists  in  tautomeric  forms, 
having  the  constitution  either  of  a  hydroxyl  compound,  enol  form,  or  of  a 
ketone,  keto  form.  The  purine  alkaloids  which  we  have  mentioned  are 
similar  hydroxyl  or  amino  derivatives  of  purine.  As  tautomeric 
compounds  they  also  exist  in  the  two  forms.  Those  which  contain 
hydroxyl  groups  have  the  enol  and  the  keto  forms,  while,  if  they  contain 
ammonia  residues  instead  of  hydroxyl,  they  have  the  corresponding 
amino  or  imino  forms.  In  the  following  formulas  only  one  tautomeric 
form  will  be  given,  viz.,  the  keto  and  the  amino. 

NH— CO  NH— CO 

/I  /I 

HC  C— NHV  O  =  C  C— NH. 

V          II             \PTT                         \           II  \rw 

^          II            ^                             \          II  ^ 

N C W  NH— C W 

Hypoxanthine  Xanthine 

*   6-Oxy  purine  2-6-Di-oxy  purine 


PURINE 

NTT         rn 

ALKALOIDS                                               QQ 

N(CH3)—  CO 

OC                    C-N(CH3)X 
II                 >CH 

AT/pTT    \          r«                                XI  " 

IN  XT-                    \-,\J 

/ 

OC                   C—  N(CH,)X 
II                  >CH 
N(CH  )     C              N 

Theobromine  and  Theophylline  (1-3) 
3-7-Di-methyl  xanthine 
or     3-7-Di-methyl  2-6-di-oxy  purine 

—  rnviT.^ 

IN  ^CxlaJ      L  W 

Caffeine 
i-3-7-Tri-methyl  xanthine 
or       i-3-7-Tri-methyl  2-6-di-oxy  purine 

NH—  CO 

H2N-C            C—  NH 

\                     >CH 

NP1             XT^ 

/ 
HC              C—  NH 
II            ,/CH 

NP            "M 

^            1\ 
Adenine 
6-Amino  purine 

\^             i\ 

Guanine 
2-Amino  hypoxanthine 

or         2-Amino  6-oxy  purine 

Synthesis  of  Xanthine. — The  synthesis  of  xanthine  which  is  the 
immediate  mother  substance  of  theobromine,  theophylline  and  caffeine 
has  been  accomplished  as  follows:  Starting  with  urea  or  carbamide, 
this  is  treated  with  cyano  acetic  acid  in  the  presence  of  phosphorus 
oxy chloride'  whereby  the  cyan  acetyl  radical  is  introduced  into  urea. 
The  cyan  acetyl  urea  by  treatment  with  sodium  hydroxide  yields  an 
isomeric  imino  compound. 


NH(H    HO)OC 


oc 


+ 


OC 


NH2 

Urea 


CN 

Cyan  acetic 
acid 


NH— CO 

I 
CH2 


NH2  CN 

Cyan  acetyl  urea 

NH-CO 


NaOH 


OC 


CH2 


NH— C  =  NH 

Imino  compound 

This  imino  derivative  with  nitrous  acid  gives  an  iso-nitroso  compound 
that  by  reduction  with  ammonium  sulphide  yields  a  di-amino  compound 
as  follows: 


Q02  ORGANIC    CHEMISTRY 

NH— CO  7NH— CO 

OC  C(H2  +  O)NOH  -  -»  OC  C  =  NOH  ^L^? 

!  I 

NH— C  =  NH  NH— C  =  NH 

Imino  compound  Iso-nitroso  compound 

NH— CO 
OC  C— NH2 

II 

NH— C— NH2 

Di-amino  compound 

The  di-amine  is  then  condensed  with  formic  acid,  the  reaction  taking 
place  in  two  steps  as  indicated  by  (i)  and  (2).  The  result  is  xanthine 
which  must  therefore  be  2-6-di-oxy  purine,  as  follows: 

NH— CO 

OC  C— NH(H  (i)  HO)— C— H       — » 

II  +  II 

NH— C— N(H2    (2)  9)  ^ 

Di-amino  compound  Formic  acid 

NH— CO 

OC'  C— NEL 

II  >H 

NH— C Nx 

Xanthine 

By  starting  this  synthesis  with  mono-methyl  urea  and  introducing 
another  methyl  radical  into  the  new  amine  groups  of  the  di-amine  the 
product  is  theobromine,  i.e.,  3-7-di-methyl  xanthine.  Similarly 
di-methyl  urea  without  further  methylation  yields  theophylline  which 
is  therefore  1-3 -di-methyl  xanthine.  Caffeine  is  obtained  by  starting 
with  di-methyl  urea  and  later  introducing  a  third  methyl  radical  in  the 
same  position  as  in  theophylline.  Caffeine  is  therefore  i-3-7-tri- 
methyl  xanthine. 


PURINE  ALKALOIDS  903 

Caffeine,  Theobromine,  Theophylline 

The  alkaloid  caffeine  is  found  in  co/ee,  tea,  and  kola.  It  is  also 
known  less  commonly  by  the  name  of  theine,  especially  as  found  in  tea. 
The  amount  present  in  coffee  and  tea  is  from  1-4.8  per  cent  in  tea  and 
1-1.5  Per  cent  in  coffee.  Caffeine  crystallizes  from  water  or  alcohol, 
m.p.  234°.  It  is  slightly  soluble  in  water,  less  so  in  alcohol  and  ether 
and  more  in  chloroform.  It  acts  as  a  weak  base.  It  may  be  prepared 
from  either  theobromine  or  from  theophylline  by  further  methylation, 
which  confirms  the  constitution  as  the  i-3-7-tri-methyl  product. 

The  two  alkaloids  theobromine  and  theophylline  are  isomeric, 
theobromine  being  the  3-7-di-methyl  xanthine  and  theophylline  the 
i-3-di-methyl  xanthine.  Theobromine  is  the  principal  alkaloid  of  the 
cocoa  bean,  Cacao  theobroma.  It  occurs  also  in  small  amounts  in  kola 
nuts  and  tea  leaves.  Theophylline  is  present  in  small  amounts  in  tea. 
They  both  resemble  caffeine  in  being  crystalline,  weak  bases. 

Physiologically  caffeine,  theobromine  and  theophylline  in  coffee  and 
tea  are  mild  stimulants,  acting  on  the  central  nervous  system.  They 
seem  to  increase  the  capacity  of  the  body  for  physical  exertion,  either 
by  acting  on  the  nerves  associated  with  psychical  functions,  or  by 
increasing  the  irritability  and  strength  of  the  muscles.  Caffeine  also 
increases  blood  pressure  and  respiration.  In  addition  to  acting  on  the 
nervous  system  these  alkaloids  also  act  on  the  kidneys,  increasing  the 
secretion  of  urine.  This  action  is  regarded  as  the  more  important. 
When  taken  as  food  caffeine  is  excreted  in  the  urine  partly  unchanged 
but  mostly  as  hypoxanthine,  xanthine  and  the  mono-  and  di-methyl 
derivatives  of  the  latter. 

Xanthine,  Hypoxanthine,  Adenine,  Guanine 

These  four  purine  alkaloids  are  much  more  important  as  animal 
than  as  plant  constituents.  Together  with  creatine,  methyl  guanidine 
acetic  acid  (p.  441),  and  creatinine,  the  anhydride  of  creatine,  they 
constitute  the  greater  part  of  what  are  termed  the  nitrogenous  extrac- 
tives of  muscular  tissue.  They  are  present  in  ordinary  beef  extract 
and  may  be  isolated  from  it.  In  addition  to  being  present  in  muscular 
tissue  they  are  mostly  found  in  the  brain,  thymus,  liver,  kidney,  spleen 
and  pancreas.  Xanthine  and  hypoxanthine  are  also  present  in  urine, 
being  the  elimination  product  of  caffeine  in  food.  Also  associated  with 


904  ORGANIC    CHEMISTRY 

them  in  urine  is  the  non-alkaloid  purine  compound  uric  acid.  Guanine 
is  found  most  abundantly  in  guano  the  excrement  of  sea  birds.  Adenine 
and  guanine  are  constituent  parts  of  the  complex  nucleic  acids  of 
living  cells.  Biologically,  they  all  are  important  products  of  meta- 
bolism. In  plants  xanthine  is  found  in  tea  but  especially  in  beet  root, 
lupine  seedlings  and  in  yeast.  Hypoxanthine  is  found  in  barley,  pota- 
toes, beet  root,  black  pepper  and  yeast.  It  is  doubtful  if  it  is  present  in 
tea.  Adenine  is  found  in  yeast,  tea  and  bamboo  shoots;  guanine  in 
yeast,  sugar  cane  and  beet  root.  The  constitution  of  each  of  these 
bases  has  been  fully  established  as  given.  Hypoxanthine  and  xan- 
thine are  related  as  the  mono-  and  di-oxy  derivatives  of  purine.  Ade- 
nine corresponds  to  hypoxan thine  being  mono-ammo  purine  while 
hypoxanthine  is  mono-oxy  purine.  Guanine  is  the  mono-amino  de- 
rivative of  hypoxanthine  or  amino  oxy  purine.  Guanine  hydrolyzes 
and  yields  both  a  urea  group  and  a  guanidine  group,  guanidine  being 
imino  urea, 

NH2 
HN=C 

NH2 

PTOMAINES 

Strictly  speaking  the  substances  known  as  ptomaines  are  not  per- 
haps alkaloids  though  in  many  respects  they  possess  the  general  prop- 
erties of  the  group.  They  do  belong  to  the  larger  group  which  includes 
the  alkaloids,  viz.,  that  of  nitrogen  bases.  Some  of  the  known  repre- 
sentatives are  highly  toxic  while  others  are  very  slightly  or  not  at  all  so 
and  do  not  show  any  marked  physiological  properties.  The  common 
knowledge  of  the  substances  is  in  connection  with  cases  of  so-called 
ptomaine  poisoning,  usually  with  some  form  of  flesh  or  rriilk  food  which 
has  been  kept  too  long  and  has  begun  to  decompose.  It  is  at  least 
possible,  however,  that  the  poisoning  is  due,  not  alone  to  ptomaines, 
but  rather  to  toxic  substances  of  bacterial  origin.  The  word  ptomaines 
comes  from  a  Greek  word  meaning  corpse  and  the  sustances  are  so  called 
because  they  are  associated  with  decomposing  flesh.  They  are  not 
themselves  products  of  bacterial  action,  i.e,  they  are  not  found  in  the 
organisms  themselves,  but  they  result  from  the  decomposition  of  pro- 


PTOMAINES 


905 


tein  .material  on  which  molds  or  bacteria  are  acting.  In  higher  forms  of 
plant  life,  such  as  the  fungi,  they  are  stored  by  the  organism,  and  in 
green  plants  they  are  found  in  the  germ  and  the  roots.  In  this  rela- 
tionship they  are  probably  nitrogen  excretion  products  of  protein  met- 
abolism and  with  them  might  be  included  the  ami-no  acids  in  general 
(p.  382),  and  even  all  amino  compounds.  In  fact  it  has  been  claimed 
that  these  simpler  nitrogen  bases,  though  many  of  them  are  not  toxic 
to  human  beings,  are  nevertheless  distinctly  toxic  to  plants  and  there- 
fore have  this  general  alkaloidal  property  of  toxicity. 

Considered  chemically  the  ptomaines  are  in  general  simpler  nitro- 
gen bases  than  most  of  the  alkaloids  and  in  most  cases  they  are  deriva- 
tives of  aliphatic  amines. 

The  exact  limits  of  the  group  of  ptomaines  are  indefinite  but  the 
compounds  following  are  usually  included. 

Putrescine,  Cadaverine 

These  two  compounds  have  been  mentioned  previously  (p.  193). 
They  are  respectively  tetra-methylene  di-amine  and  penta-methylene 
di-amine. 

CH2 

/\ 

H2C CH2  H2C        CH2 

H2C        CH2  H2C        CH2 

I      !  II 

H2N        NH2  H2N        NH2 

Putrescine  Cadaverine 

The  relationship  of  these  two  compounds  to  pyrrolidine  (p.  855)  and 
piperidine  (p.  857),  which  they  yield  by  loss  of  ammonia  with  the 
formation  of  a  heterocyclic  ring,  has  been  considered.  Both  of  these 
bases  are  common  putrefaction  products,  of  animal  bodies  as  indicated 
by  their  names.  They  both  result  from  bacterial  action  on  di-amino 
acids  by  decarboxylation,  i.e.,  loss  of  CO2,  and  they  probably  are  pro- 
duced in  this  way  during  putrefaction.  Besides  occurring  in  decom- 
posed flesh,  they  have  been  found  also  in  ergot,  in  some  varieties  of 
cheese,  in  pathological  urine  and  in  putrified  soy  beans, 
both  non-toxic  to  animals. 


906  ORGANIC    CHEMISTRY 

Ergot  Base,  Hordenine 

Two  bases  found  in  barley  germs  and  in  ergot  are  closely  related  com- 
pounds. Ergot  is  a  fungus  growth  occurring  on  cereals,  especially  rye. 
From  it  several  alkaloid  substances  have  been  isolated.  One  of  these 
has  been  shown  to  be  para-hydroxy  phenyl  ethyl  amine. 

/OH  (p) 

C6H4<^  Ergot  base 

CH2—  CH2NH2 

It  is  to  this  substance  that  the  principal  physiological  action  of  ex- 
tracts of  ergot  are  due  in  exerting  a  strong  pressor  action  on  the  circu- 
lation thus  raising  the  blood  pressure.  Besides  being  found  in  ergot 
this  compound  is  found  also  in  cheese  and  in  putrid  meat. 

It  has  been  synthesized  from  tyrosine,  para-hydroxy  phenyl  alpha  - 


amino  propionic  acid, 

CH2—  CH(NH2)—  COOH.    It  is  prob- 
ably derived  from  this  amino  acid  during  the  putrefaction  of  meat. 

OH 

C6H4<f  Hordenine,  p-Hydroxyphenyl-ethyldi- 

XCH2—  CH2N(CH3)2  methyl  amine. 

Hordenine  is  the  name  of  the  related  base  present  in  the  germs  of 
barley,  Hordeum  vulgare.  It  has  been  proven  to  have  the  constitution 
of  a  di-methyl  derivative  of  the  ergot  base,  as  above. 

Lecithin,  Choline,  Neurine 

The  base  choline  is  the  mother  substance  of  three  other  bases,  viz., 
neurine,  muscarine  and  betaine.  Choline  is  very  widely  distributed 
having  been  found  in  fifty  or  more  animal  tissues  and  plants.  The 
occurrence  of  most  interest  is  as  a  constituent  part  of  a  substance 
known  as  lecithin.  Although  not  itself  a  member  of  this  group  of 
nitrogen  bases,  lecithin  will  be  considered  now  in  connection  with 
choline.  Lecithin,  or  the  lecithins,  belongs  to  the  group  of  compounds 
known  as  phospho-lip-ines.  This  name  signifies  the  three  primary 
constituents,  viz.,  a  phosphoms-contammgfat  possessing  basic  or  amino 
properties.  On  complete  hydrolysis  lecithin  yields  four  products. 


Lecithin 


hydrol- 
ysis 


LECITHIN     CHOLINE     NEURINE  907 

(1)  Glycerol. 

(2)  A  fatty  acid,  usually  palmitic,  stearic  or  oleic 
acid. 

(3)  Phosphoric  acid. 


(4)  Choline,  an  amine  base. 

Further  study  has.  shown  that  in  lecithin  the  tri-hydroxy  alcohol  gly- 
cerol  has  two  hydrogens  only  replaced  by  fatty  acid  radicals,  while  the 
third  is  similarly  replaced  by  the  phosphoric  acid  radical.  In  case  the 
fatty  acid  is  stearic  acid  the  lecithin  will  be  a  glyceryl  di-stearate 
mono-phosphate  ester.  Phosphoric  acid  being  tri-basic,  with  only 
one  of  its  acid  groups  neutralized  by  the  glycerol,  has  one  of  the  re- 
maining groups  similarly  neutralized  by  the  base  choline.  In  this 
base  there  is  present  an  hydroxy-ethyl  group  which,  as  an  alcohol,  is 
the  ester  forming  group  with  one  of  the  remaining  acid  groups  of  the 
phosphoric  acid.  The  constitution  of  choline,  which  is  essential  to 
the  complete  constitution  of  lecithin,  has  been  established  by  several 
syntheses  one  of  which  is  from  tri-methyl  amine  and  ethylene  oxide 
in  water  solution. 

H.C,  H.C,          OH 

CH2—  CH2    ±±T    H3CAN<^ 

H8Cr        XCH2—  CH2—  OH 

Tri-methyl  Ethyl  ene  Choline 

amine  oxide 

Choline  is  thus  a  quaternary  ammonium  hydroxide  base,  viz.,  tri-methyl 
hydroxy-ethyl  ammonium  hydroxide,  as  in  the  formula  just  given. 
The  constitution  of  lecithin  is  therefore  as  follows: 
CH2OOC—  Ci7H35 

I 
CHOOC—  Ci7H35 

OH 

/  Lecithin 

CH,00—  P  =  0  HO 


\     / 

OCH2—  CH2-    -N^-CH, 
NCH3 


There  are  different  lecithins,  due  to  the  particular  fatty  acid  or  ;u  id- 
present,  the  name  being  that  of  a  group  rather  than  of  an  individual 


QO8  ORGANIC    CHEMISTRY 

compound.  Lecithin  is  a  normal  constituent  of  all  living  cells.  Its 
most  common  and  abundant  sources  are  in  egg  yolk,  fish  ova,  the  brain, 
nerves  and  other  animal  tissues.  It  is  a  soft  fat-like  substance  soluble 
in  chloroform,  ether,  alcohol,  benzene  and  carbon  di-sulphide.  From 
alcoholic  solution  it  crystallizes  in  plates.  As  choline  is  a  constituent 
part  of  lecithin,  it  is  thus  found  in  combination  in  all  those  plant  and 
animal  tissues  where  lecithin  itself  is  present.  It  has  been  found  free 
in  certain  seeds  and  in  the  cerebro-spinal  fluid  in  disease. 

Neurine,  the  third  substance  mentioned  in  this  group,  is  a  nitrogen 
base  analogous  to  choline,  being  related  to  it  as  ethene  is  related  to 
ethyl  alcohol,  i.e.,  neurine  is  tri-m ethyl  vinyl  ammonium  hydroxide, 
as  follows: 

H3C,  OH 

H3C-^N<^  Neurine 

H3C  CH  =  CH2 

Neurine  is  a  product  of  the  putrefaction  of  flesh.  It  has  been  prepared 
synthetically  from  tri-methyl  amine  and  ethylene  di-bromide,  and  also 
from  choline.  The  constitution  as  above  given  is  thus  thoroughly  es- 
tablished. 

Physiologically  choline  is  primarily  a  depressant  on  the  circulation 
but  is  not  strongly  toxic.  Neurine  is  similar  in  its  action  and  10  to  20 
times  as  toxic  as  choline. 

Muscarine  and  Betaine 

These  two  bases  are  related  to  choline  and  their  constitution  has 
been  accepted  as  that  of  the  corresponding  hydrated  aldehyde,  in  the  case 
of  muscarine,  and  the  acid  anhydride  in  the  case  of  betaine.  The 
formulas  of  the  three  compounds  show  the  relationship. 


,OH 
HgCT         NCH2— CH2OH        H3(T         NCH2— CH<" 

XOH 


Choline  Muscarine 

(alcohol)  (aldehyde 

hydrate) 


HsC^N/        \CO 
H.CT  CH2 

Betaine 

(acid  anhydride) 


MUSCARINE  BETAINE  gO9 

Muscarine  is  especially  interesting  in  that  it  is  the  poisonous  con- 
stituent of  the  deadly  toad-stool  Aminita  muscaria  and  of  other  poison- 
ous fungi.  It  is  a  soluble,  crystalline,  tasteless  compound  of  extreme 
toxicity. 

Betaine  derives  its  name  from  the  fact  that  it  occurs  in  the  molasses 
obtained  from  beets,  being  therefore  present  in  the  beet  root.  It 
is  somewhat  widely  distributed  in  plants  but  not  so  widely  as  choline. 
Betaine  is  non-toxic  and  there  is  even  possibility  that  it  may  be  used 
as  a  food  material  by  animals.  Like  lecithin  it  is  not  an  individual,  but 
represents  rather  a  group  of  compounds  characterized  by  the  dis- 
tinctive group 

\  /°\ 

-)N<          ">CO 


In  the  foregoing  discussion  of  the  alkaloids  no  attempt  has  been 
made  to  make  the  study  at  all  exhaustive  or  complete.  Only  those 
individual  alkaloids  have  been  considered  which  are  either  of  general 
common  interest  in  their  properties  or  use  as  medicines  or  that  are 
related  pretty  directly,  in  their  constitution,  to  other  compounds 
which  we  have  studied.  The  chemistry  of  the  alkaloids  deals  not 
only  with  their  constitution,  which  is  the  main  point  in  the  present 
study,  but  even  more  with  their  biological  relationships,  both  as  to 
their  origin  and  function  in  plants,  and  their  physiological  action  upon 
animals.  All  of  these  questions  have  been  very  inadequately  treated. 
For  further  information  the  student  is  referred  to  larger  books  dealing 
especially  with  this  most  interesting  and  important  group. 

Conclusion 

With  the  alkaloids  our  study  of  organic  chemistry  is  completed  in  so 
far  as  the  purpose  of  this  book  requires.  Not  all  compounds  or  even 
all  groups  of  compounds  have  been  considered,  but  with  those  which 
have  occupied  us  from  the  beginning,  the  student  will  have  as  a  basis 
for  further  study  a  rather  comprehensive  knowledge  of  the  most 
important  and  outstanding  relationships  and  of  individual  compounds 
or  groups  representing  the  immense  field  of  organic  chemistry,  a 
branch  of  the  science  of  chemistry  which  has  had  a  phenomenal  develop- 
ment for  nearly  a  century  and  which  is  remarkable  for  its  close  contact, 
not  only  with  pure  science,  but  also  with  industrial  and  economic 
problems  and  with  life  itself. 


QIO  ORGANIC    CHEMISTRY 

BOOKS  OF  REFERENCE 
Encyclopedias  and  Dictionaries 

BEILSTEIN,   F.:   Handbuch  der  Organischen   Chemie,   3d  ed.   with   Supplement, 

1893-1906. 

RICHTER,  M.  M.rLexikon  der  Kohlenstoff-Verbindungen,  1910-12. 
THORPE,  T.  E.:  Dictionary  of  Applied  Chemistry,  1912. 
ULLMANN,  F.:  Enzyklopedie  der  technischen  Chemie,  vol.  1-3,  1914-1916. 

History  and  Theory 

HENRICH,  F.:  Theorien  der  Organischen  Chemie,  1912. 
LACHMAN,  A.:  The  Spirit  of  Organic  Chemistry,  1899. 
Moore,  F.  J.:  History  of  Chemistry,  1918. 
POPE,  F.  G.:  Modern  Research  in  Organic  Chemistry,  1913. 
SCHORLEMMER,  C. :  Rise  and  Development  of  Organic  Chemistry,  1894. 
STEWART,  A.  W.:  Recent  Advances  in  Organic  Chemistry,  1911. 
THORPE,  T.  E.:  Essays  on  Historical  Chemistry,  1894. 

Textbooks 

ABDERHALDEN,  E.:Lehrbuch  der  Physiologischen  Chemie,  1909. 

BERNTHSEN — McGowAN:  Textbook  of  Organic  Chemistry,  1896. 

CLARK,  H.  T.:  Introduction  to  the  Study  of  Organic  Chemistry,  1914. 

COHEN,  J.  B.:  Organic  Chemistry  for  Advanced  Students,  1910-13,  1919. 

COHEN,  J.  B.:  Theoretical  Organic  Chemistry,  1907. 

DIELS,  O.:  Einfiihrung  in  die  Organische  Chemie,  1907. 

HASS,  P.— HILL,  T.  G.:  The  Chemistry  of  Plant  Products,  1913. 

HASKINS,  H.  D.:  Organic  Chemistry,  1917. 

HOLLEMAN,  A.  F. — WALKER,  A.  J.:  Textbook  of  Organic  Chemistry,  1911. 

MATHEWS,  A.  P.:  Physiological  Chemistry,  1915. 

McCoLLUM,  E.  V. :  Textbook  of  Organic  Chemistry  for  Students  of  Medicine  and 

Biology,  1916. 

MEYER,  V. — JACOBSON,  P.:Lehrbuch  der  Organischen  Chemie,  1893. 
MOLINARI,  E. — POPE,  T.  H.:  General  and  Industrial  Chemistry,  Organic,  1913. 
NOYES,  W.  A.:  Text  Book  of  Organic  Chemistry,  1910. 
NORRIS,  J.  F. :  The  Principles  of  Organic  Chemistry,  1912. 
PERKIN,  W.  H. — KIPPING,  F.  S.:  Organic  Chemistry,  1911. 
PLIMMER,  R.  H.  A.:  Practical  Organic  and  Bio-chemistry,  1915. 
REMSEN,  IRA:  Introduction  to  the  Study  of  Compounds  of  Carbon  or  Organic 

Chemistry,  5th  ed. 

RICHTER — SMITH:  Chemistry  of  Carbon  Compounds. 
ROGERS,  A.:  Industrial  Chemistry,  1915. 
STODDARD,  J.  T.:  Introduction  to  Organic  Chemistry,  1919. 

Laboratory  Manuals 

BARNETT,  E.  DEB.:  Preparation  of  Organic  Compounds,  1912. 
FAY,  I.  W.:  The  Chemistry  of  Coal  Tar  Dyes,  1911. 


BOOKS    OF    REFERENCE  911 

FISCHER,  E.:  Anleitung  zur  Darstellung  Organischer  Praparate,  1893. 

GATTERMANN,  L. — SCHOBER,  W.  G.:  Practical  Methods  of  Organic  Chemistry,  1914. 

HAWK,  P.  B.:  Practical  Physiological  Chemistry,  1918,  6th  ed. 

HOLLEMAN,  A.  F. — WALKER,  A.  J. :  Laboratory  Manual  of  Organic  Chemistry,  1913. 

JONES,  L.  W. :  A  Laboratory  Outline  of  Organic  Chemistry,  1911. 

LEVY,  S. — BISTRZYCKI:  Anleitung  zur  Darstellung  organisch-chemischer  Pritparate, 

1895. 

MANDEL,  J.  A.:  Handbook  for  the  Bio-chemical  Laboratory,  1896. 
MATTHEWS,  J.  M.:  Laboratory  Manual  of  Dyeing  and  Textile  Chemistry,  1009. 
MOORE,  F.  J. :  Experiments  in  Organic  Chemistry,  1915. 
MULLIKEN,  S.  P.:  The  Identification  of  Pure  Organic  Compounds,  1911-1916. 
NORRIS,  J.  F.:  Experimental  Organic  Chemistry,  1915. 
NOYES,  A.  A. — MULLIKEN,  S.  P. :  Laboratory  Experiments  on  Class  Reactions  and 

Identification  of  Organic  Compounds,  1898. 
NOYES,  W.  A.:  Organic  Chemistry  for  the  Laboratory,  1911. 
ORNDORFF,  W.  R. :  A  Laboratory  Manual  of  Organic  Chemistry,  5th  ed. 
STEEL,  M.:  Laboratory  Manual  of  Organic  Chemistry  for  Medical  Students,  1916. 

Monographs  and  Books  on  Special  Subjects 
ALLEN,  A.  H. :  Commercial  Organic  Analysis,  5th  ed. 
ARMSTRONG,  E.  F.:  The  Simpler  Carbohydrates  and  the  Glucosides,  1914. 
BARGER,  G. :  The  Simpler  Natural  Bases,  1914. 

BRACHVOGEL,  J.  K.:  Industrial  Alcohol,  its  Manufacture  and  Uses,  1907. 
CAIN,  J.  C—  THORPE,  J.  P.:  The  Synthetic  Dyestuffs,  1913. 
EULER,  H.— POPE,  T.  H.:  General  Chemistry  of  the  Enzymes,  1912. 
GILDEMEISTER  &  HOFFMANN — KREMERS:  The  Volatile  Oils,  2d  ed.,  1913. 
HARDEN,  A.:  Alcoholic  Fermentation,  1911. 
HEUSLER,  F.— POND,  E.  J. :  Chemistry  of  Terpenes,  1902. 
HOLDE,  D.— MUELLER,  E.:  Examination  of  Hydrocarbon  Oils,  1915. 
KNOX,  J. :  The  Fixation  of  Atmospheric  Nitrogen,  1914. 
LEATHES,  J.  B.:  The  Fats,  1910. 
LEWKOWITSCH,  J.:  Chemical  Technology  and  Analysis  of  Oils,  Fats  and  Waxes, 

5th  ed.,  1913. 

LING,  A.  R.:  The  Polysaccharides,  1908. 
MACLEAN,  H.:  Lecithin  and  Allied  Substances,  1918. 

MARSHALL,  A. :  Explosives,  their  Manufacture,  Properties,  Tests  and  History,  1915 
MARSHALL^  A.:  A  Short  Account  of  Explosives,  1917. 
MAY,  PERCY:  The  Chemistry  of  Synthetic  Drugs,  1911. 
MORGAN,  G.  T.:  Organic  Compounds  of  Arsenic  and  Antimony,  1918. 
OSBORNE,  T.  B.:  Proteins  of  the  Wheat  Kernel,  1907- 
OSBORNE,  T.  B.:  The  Vegetable  Proteins,  1909. 
PRIDEAUX:  The  Theory  and  Use  of  Indicators,  1917- 
PICTET  A  -BIDDLE,  H.  C. :  The  Vegetable  Alkaloids,  1904. 
PLIMMER,  R.  H.  A.:  The  Chemical  Constitution  of  Proteins,  1908 
PORRITT/B.  D.:  The  Chemistry  of  Rubber,  1913- 
REDWOOD,  B.:  Petroleum  and  Its  Products,  1896. 


912  ORGANIC    CHEMISTRY 

SANFORD,  P.  G.:  Nitro  Explosives,  1906. 

SCHRYVER,  S.  B.:  The  General  Characters  of  Proteins,  1912. 

SHERMAN,  H.  C. :  Organic  Analysis,  1912. 

WAGNER,  F.  H.:  Coal  Gas  Residuals,  1914. 

WREN,  H. :  The  Organo-metallic  Compounds  of  Zinc  and  Magnesium,  1913. 

WOOD,  J.  K.:  The  Chemistry  of  Dyeing,  1913. 


APPENDIX 

THE  SEPARATION,  PURIFICATION,  IDENTIFICATION,  ANALY- 
SIS AND  DETERMINATION  OF  THE  MOLECULAR  WEIGHT  OF 
ORGANIC  COMPOUNDS 

SEPARATION  AND  PURIFICATION 

In  the  preparation  of  an  organic  compound,  the  product  obtained 
must  be  separated  and  purified.  If  it  is  a  known  compound,  it  may 
then  be  identified;  while,  if  it  is  unknown,  it  must  be  analyzed  and  its 
molecular  weight  determined. 

Separation  of  Liquids. — The  methods  of  separation  are  of  two 
general  types,  one  for  liquids  and  the  other  for  solids.  A  liquid  prod- 
uct may  consist  of  the  entire  reaction  mixture,  or  it  may  be  obtained 
as  a  distillate.  The  product  may  contain  acid  or  alkali  or  it  may  be 
mixed  with  water,  alcohol  or  other  liquids  used  in  the  reaction  or  ob- 
tained as  secondary  products. 

If  the  mixed  liquid  product  does  not  separate  into  two  distinct 
layers  of  non-miscible  liquids,  such  separation  is  sometimes  brought 
about  by  the  addition  of  water.  The  two  liquids  are  then  separated 
by  means  of  a  separatory  funnel  and  the  one  containing  the  desired 
product  is  washed  with  water  to  free  it  from  any  acid  or  alkali  present. 
The  washing  is  accomplished  by  adding  about  an  equal  volume  of 
water,  shaking  thoroughly  and  then  separating  a  second  time.  The 
washing  and  separating  may  need  to  be  repeated  several  times.  If  the 
crude  separated  product  is  known  to  be  strongly  acid,  or  to  contain 
substances,  e.g.,  bromine,  easily  removed  by  alkali,  then  a  little  alkali 
is  added  with  the  first  wash  water.  Similarly,  if  the  crude  product  is 
known  to  be  strongly  alkaline,  a  little  acid  may  be  used  in  the  first 
wash  water.  When  the  product  is  thoroughly  washed,  the  water,  still 
held  as  a  physical  mixture,  is  removed  by  the  addition  of  a  dehydrating 
agent,  such  as  concentrated  sulphuric  acid,  anhydrous  calcium  chloride, 
anhydrous  potassium  carbonate  or  solid  potassium  hydroxide.  In  some 
cases,  the  drying  may  be  accomplished  by  placing  the  product  in  a 
desiccator.  After  standing  over  the  dehydrating  agent  until  the 

913 

58 


914  APPENDIX 

watery,  opaque  liquid  is  clear,  it  is  separated  by  decantation  and  the 
practically  pure,  dry  product  is  then  distilled. 

If  the  product  finally  obtained  is  an  individual  compound  it  will 
distil  at  approximately  a  constant  temperature  which  is  the  boiling- 
point  of  the  compound.  If  the  product  is  a  mixture  of  two  compounds 
that  can  be  separated  by  fractional  distillation,  this  method  is  then 
used  as  in  the  case  of  the  separation  of  alcohol  and  water,  which  is  a 
common  laboratory  exercise  illustrating  this  process.  It  usually 
results  that  compounds  so  separated  are  only  partially  pure,  each  being 
mixed  with  a  little  of  the  other.  In  some  cases,  two  compounds  can 
not  be  separated  in  this  way,  because  their  boiling-points  are  too  close 
together.  By  conversion  into  derivatives,  e.g.,  esters,  the  boiling- 
points  of  which  lie  farther  apart,  fractional  distillation  may  be  made 
possible.  The  conditions  of  distillation  may  also  vary  as  some  com- 
pounds must  be  distilled  under  diminished  pressure. 

Separation  of  Solids. — The  separation  of  solid  compounds  involves 
the  process  of  crystallization.  The  solid  compound,  obtained  as  the 
result  of  a  reaction,  may  be  insoluble  in  the  reaction  mixture  or  it  may 
be  soluble.  In  case  it  is  insoluble  it  is  filtered  off  and  washed,  the  style 
of  filtration  differing  according  to  the  nature  of  the  product.  A  crystal- 
line residue  is  usually  filtered  on  a  Buchner  funnel  with  the  aid  of  suc- 
tion but,  if  the  residue  is  fine  and  packs,  it  is  better  to  filter  through 
an  ordinary  filter  paper  or  through  a  fluted  paper.  The  washed  residue 
is  then  dissolved  in  an  appropriate  solvent  and  crystallized.  Some- 
times the  insoluble  residue  consists  of  the  desired  compound  mixed  with 
other  insoluble  compounds.  In  this  case  the  residue  is  extracted  with 
an  appropriate  solvent  and  the  compound  crystallized  from  the  solution. 

If  the  desired  compound  is  soluble  in  the  reaction  liquid,  the  solution 
is  separated  from  any  insoluble  residue  by  filtration,  usually  through  a 
fluted  filter  paper.  The  solution  containing  the  compound  is  then 
ready  for  crystallization. 

Crystallization. — To  crystallize  a  soluble  compound  out  of  its 
solution,  the  solution  is  evaporated,  not  too  rapidly,  to  incipient 
crystallization,  the  hot  solution  filtered  and  the  clear  filtrate  allowed  to 
cool.  By  slow  cooling  from  incipient  crystallization  large  crystals 
are  usually  obtained,  while  evaporation  of  the  solution  beyond  incipient 
crystallization,  followed  by  rapid  cooling,  usually  yields  a  more  abund- 
ant product  of  purer  and  finer  crystals.  After  cooling,  the  crystalline 


APPENDIX 

product  is  filtered  on  a  Buchner  funnel,  with  suction,  the  crystals 
washed  slightly  with  fresh  solvent  and,  if  necessary,  recrystallized 
one  or  more  times  in  order  to  secure  a  pure  product.  The  ease  of 
solubility  of  the  compound  in  the  solvent  used  affects  the  procedure. 
If  a  compound  is  much  more  soluble  in  hot  solvent  than  in  cold,  the 
mere  cooling  of  the  hot  solution  may  yield  abundant  product  and  the 
greater  part  of  it.  If,  however,  the  compound  is  almost  as  soluble  in 
cold  solvent  as  in  hot,  the  solution  must  be  evaporated  in  order  to 
bring  about  crystallization. 

After  a  crystalline  product  of  sufficient  purity  has  been  obtained  the 
crystals  must  be  dried  to  remove  external  moisture  or  other  solvent. 
This  is  accomplished  either  by  warming,  by  allowing  the  crystals  to 
stand  in  a  desiccator,  by  pressing  them  between  folds  of  filter  paper,  by 
placing  them  on  a  porous  unglazed  plate,  or  by  simply  exposing  them 
to  warm  dry  air.  The  amount  of  heat  allowable  in  drying  a  crystalline 
compound  depends  upon  its  melting  point  and  upon  the  presence  or 
absence  of  water  of  crystallization. 

After  pure  dry  crystals  have  been  obtained  they  are  then  ready  for 
identification,  analysis  or  preservation. 

IDENTIFICATION 

The  identification  of  an  organic  compound,  in  case  it  is  of  known 
composition,  constitution  and  properties,  involves  simply  the  deter- 
mination of  its  physical  constants.  The  physical  constants,  the  deter- 
mination of  which  is  usually  sufficient  for  the  purpose,  are  the  melting- 
point,  the  boiling-point  and  the  specific  gravity. 

Determination  of  Melting-Point. — The  determination  of  the 
melting  point  of  a  solid  compound,  usually  obtained  in  a  crystalline 
form,  is  accomplished  by  introducing  a  very  little  of  the  finely  powdered 
substance  into  a  fine,  thin-walled  capillary  tube,  known  as  a  melting- 
point  tube.  This  tube  is  then  fixed  in  close  contact  with  the  bulb  of  a 
thermometer  and  the  two  immersed,  to  the  depth  of  about  one-half 
inch  above  the  thermometer  bulb,  in  sulphuric  acid  or  some  other 
liquid,  which  is  then  gradually  heated  to  the  known  or  supposed  melting- 
point.  The  temperature  reading  of  the  thermometer,  at  the  instant  the 
compound  within  the  capillary  melts,  is  the  melting-point.  The  heating 
is  often  accomplished  in  a  small  round-bottom  flask  which  is  clamped 


916  APPENDIX 

by  the  neck  so  that  it  may  be  warmed  by  the  small  flame  of  a  burner 
held  in  the  hand  and  moved  around  slowly.  A  better  form  of  apparatus 
is  the  special  melting-point  bulb  devised  so  as  to  secure  slow,  uniform 
heating  of  the  thermometer  and  the  compound  in  the  affixed  melting- 
point  capillary  tube. 

If  the  compound  melts  sharply,  within  a  range  of  a  degree  or  two 
and  within  a  degree  or  two  of  the  theoretical  melting-point,  it  is  usually 
sufficient  proof  of  identity.  Repeated  determinations  should  be  made 
to  insure  good  results. 

In  the  case  of  some  compounds  with  low  melting-point  and  of  fats 
and  oils,  which  are  not  individual  compounds,  the  temperature  at 
which  the  liquid  substance  solidifies  is  determined  rather  than  the 
melting-point.  This  is  termed  the  solidification-point  or  freezing-point. 

Determination  of  Boiling-Point. — It  is  not  usual  to  determine  both 
the  melting-point  and  the  boiling-point  of  the  same  compound,  for  one 
of  the  two  often  comes  outside  of  the  range  of  ordinary  laboratory 
operations.  The  melting-point  is  generally  determined  in  the  case 
of  compounds  that  are  solid  at  ordinary  temperatures,  and  the  boiling- 
point  in  the  case  of  those  that  are  liquid. 

The  boiling-point  of  a  liquid  compound  is  determined  by  simply 
distilling  a  little  of  the  pure  dry  compound  using  a  small  distilling 
flask  with  a  thermometer  carefully  placed  in  the  neck  of  the  flask  so 
that  the  top  of  the  mercury  bulb  is  just  below  the  outlet.  Wrapping 
the  neck  of  the  flask  and  the  thermometer  with  asbestos  paper,  to 
prevent  sudden  cooling  by  drafts  of  air,  is  a  precaution  that  insures 
more  accurate  results. 

Determinations  so  made  are  subject  to  corrections  for  the  thermo- 
meter and  for  the  fact  that  part  of  the  thermometer  column  is  outside 
of  the  vapor  of  the  boiling  liquid.  Boiling-points  described  as  "cor- 
rected" have  had  the  above  corrections  made.  As  the  boiling-point 
of  a  liquid  varies  with  the  pressure  it  is  also  necessary  to  designate  the 
barometric  pressure  under  which  the  determination  is  made. 

Determination  of  Specific  Gravity. — The  determination  of  the 
specific  gravity,  usually  in  the  case  of  liquids  only,  is  made  by  means  of 
a  pycnometer  or  specific  gravity  bottle.  The  pycnometer  is  filled  with 
the  liquid,  at  a  definite  temperature,  and  weighed.  The  weight  of 
the  pycnometer  empty,  and  the  weight  of  it  when  filled  with  water  at  a 
definite  temperature,  must  also  be  known  or  must  be  determined. 


APPENDIX  917 

From  the  data  thus  obtained  the  specific  gravity  may  be  calculated 
from  the  equation: 

Wt.  Vol.  of  Liquid 
=  Wt.  equal  Vol.  of  Water 

The  temperature  at  which  the  water  is  weighed  should  be  4°,  the 
temperature  of  its  maximum  density,  but  it  may  be  some  other.  The 
temperature  at  which  the  liquid  is  weighed  may  be  4°  also,  or  it  may 
be  any  arbitrary  temperature,  e.g.,  15°,  which  is  a  commonly  accepted 
standard.  These  temperatures  should  always  be  given  as  part  of  the 

Q 

recorded  constant  and  are  expressed  as  follows:  Sp.  Gr.  — V  means 

4 
that  the  temperature  of  the  liquid  was  15°  and  that  of  the  water  was 

o  o 

4°.    Sp.  Gr.  -*s  or    0  means  that  the  temperature  of  the  two  liquids 

*5         4 
was  the  same  and  as  indicated. 

ANALYSIS 

In  organic  compounds,  the  elements  ordinarily  determined  by 
what  is  termed  ultimate  analysis  are  carbon,  hydrogen,  oxygen,  nitro- 
gen, sulphur  and  one  of  the  halogens.  Other  elements  may  some- 
times be  present  but  we  shall  not  consider  their  determination  here. 

Qualitative  Tests. — To  test  an  organic  compound  qualitatively  is  a 
simple  matter.  The  presence  of  carbon  which,  of  course,  is  found  in  all 
organic  compounds,  is  proven  by  heating  some  of  the  compound  with 
copper  oxide,  or  in  an  atmosphere  of  oxygen  gas.  Carbon  dioxide  is 
thereby  formed  and  is  identified  by  absorption  in  lime  water  with  the 
production  of  a  precipitate  of  calcium  carbonate.  A  still  simpler 
method  is  to  heat  the  compound  slowly  on  a  piece  of  platinum  foil. 
Charring  and  then  burning  proves  the  presence  of  carbon;  no  ash 
being  left,  unless  the  compound  is  a  metal  salt  or  an  organo-metallic 
compound. 

The  same  method  as  the  first  one  given  above  is  used  for  the  detec- 
tion of  hydrogen,  its  presence  being  proven  by  the  formation  of  water 
as  the  result  of  oxidation. 

Nitrogen  is  tested  for  by  either  of  two  methods.  A  little  of  the  dry 
compound  is  mixed  with  an  equal  amount  of  dry  soda-lime  and  heated 
in  a  small  tube  until  charring  and  then  complete  decomposition  takes 
place.  The  formation  of  ammonia  gas,  detected  by  means  of  a  piece  of 


gi8  APPENDIX 

red  litmus  paper  held  in  the  mouth  of  the  tube,  proves  the  presence  of 
nitrogen.  The  other  method  is  known  as  the  cyanide  test.  When  an 
organic  nitrogen  compound  is  fused  with  metallic  sodium,  sodium 
cyanide  is  formed.  By  heating  the  acidified  solution  of  the  fused  mass 
with  a  ferrous  iron  salt,  sodium  ftrro  cyanide  is  produced  and  the  pres- 
ence of  this  is  shown  by  the  formation  of  a  blue  precipitate  of  Prussian 
blue  on  the  addition  of  a  little  ferric  chloride  solution. 

Sulphur,  in  the  unoxidized  condition,  is  tested  for  by  heating  the 
compound  with  metallic  sodium  or  with  sodium  carbonate,  by  which 
treatment  the  sulphur  is  converted  into  sodium  sulphide.  If  the  fused 
product  is  placed  on  a  silver  coin  and  moistened,  a  spot  of  silver  sulphide 
will  be  produced.  The  fused  mass  may  also  be  dissolved  in  water, 
neutralized  with  nitric  acid,  and  a  little  lead  acetate  solution  added. 
The  formation  of  a  black  precipitate  of  lead  sulphide  proves  the  presence 
of  sulphur.  These  tests  are  applicable  only  in  case  the  sulphur  is  in  an 
unoxidized  form.  To  test  for  sulphur  in  either  the  oxidized  or  un- 
oxidized form  a  little  of  the  compound  is  boiled  with  strong  nitric  acid. 
or  is  heated  with  sodium  peroxide.  This  treatment  converts  the  sul- 
phur into  the  form  of  sulphuric  acid  or  a  sulphate,  either  of  which  will 
yield  a  white  precipitate  of  barium  sulphate  when  tested  with  barium 
nitrate  in  the  presence  of  nitric  acid. 

The  halogens,  chlorine,  bromine,  and  iodine,  are  tested  for  by  heating 
the  compound  with  lime,  free  of  halides,  acidifying  the  solution  of  the 
fused  mass  with  nitric  acid  and  testing  with  silver  nitrate.  A 
precipitate  of  silver  halide  proves  the  presence  of  a  halogen. 

In  the  study  of  organic  compounds  resulting  from  organic  laboratory 
preparations,  it  is  seldom  necessary  to  carry  out  a  complete  qualitative 
analysis  as  the  elements  present  are  generally  known. 

Quantitative  Determination. — The  quantitative  determination,  of 
the  amount  of  each  element  present  in  an  organic  compound,  is  ordi- 
narily termed  organic  combustion  as  combustion  or  oxidation  takes  place 
in  all  of  the  determinations. 

Carbon  and  Hydrogen  by  Combustion. — When  an  organic  com- 
pound is  heated  in  the  presence  of  copper  oxide  or  in  a  stream  of  pure 
oxygen  gas,  it  is  oxidized  or  burned.  If  the  oxidation  is  complete,  all 
of  the  carbon  of  the  compound  is  converted  into  carbon  dioxide  and  all 
of  the  hydrogen  into  water.  The  combustion  is  carried  out  in  a  long 
tube  of  hard  glass,  or  of  fused  quartz,  known  as  a  combustion  tube. 


APPENDIX 

The  tube  is  heated  in  either  a  gas  or  an  electric  combustion  furnace. 
Details  as  to  filling  the  tube  and  heating  will  not  be  given  here  as  they 
pertain  more  properly  to  text  books  of  analytical  chemistry.  The 
products  of  oxidation  pass  from  the  combustion  tube  through  apparatus 
for  the  absorption  of  gases;  first  for  the  absorption  of  water  and  then 
of  the  carbon  dioxide.  The  absorption  of  water  takes  place  in  tubes 
containing  properly  prepared,  non-basic  anhydrous  calcium  chloride 
or  pure  concentrated  sulphuric  acid.  The  increase  in  the  weight  of  the 
tube  during  the  combustion  gives  us  the  amount  of  water  produced,  and 
from  this  the  amount  of  hydrogen  may  be  calculated.  The  absorption 
of  carbon  dioxide  takes  place  in  potash  bulbs  (Liebig  bulbs  or  some 
modification  of  them)  which  contain  a  solution  of  potassium  or  sodium 
hydroxide,  of  proper  concentration.  The  increase  in  the  weight  of 
these  bulbs  gives  the  amount  of  carbon  dioxide  produced,  from  which 
the  amount  of  carbon  may  be  calculated. 

Nitrogen  by  the  Dumas  Method.— Two  methods  are  used  for  the 
determination  of  nitrogen,  viz.,  the  Dumas  method  and  the  Kjeldahl 
method.  The  Dumas  method  is  also  known  as  the  absolute  method 
and  is  a  dry  combustion  operation  similar  to  the  one  for  carbon  and 
hydrogen.  When  an  organic  compound  containing  nitrogen  is  heated, 
in  the  presence  of  copper  oxide  or  pure  oxygen  gas,  the  nitrogen  is 
converted  into  some  of  its  oxides.  Before  leaving  the  heated  combus- 
tion tube  the  products  of  oxidation  are  passed  over  coils  of  pure  reduced 
copper.  The  oxides  of  nitrogen  are  reduced  .by  the  copper  and  free 
nitrogen  gas  is  the  final  product.  The  nitrogen  gas  is  collected  in  a 
special  gas  burette  which  contains  a  solution  of  potassium  or  sodium 
hydroxide  to  absorb  carbon  dioxide.  After  the  combustion  is  com- 
pleted the  pure  nitrogen  gas  is  transferred  from  the  burette  to  a  eudio- 
meter tube,  measured  under  atmospheric  conditions,  the  volume 
reduced  to  standard  conditions  of  temperature  and  pressure  (o°  and 
760  mm.),  and,  from  the  final  volume  of  pure  nitrogen  gas,  the  weight  of 
nitrogen  is  calculated. 

Nitrogen  by  the  Kjeldahl  Method. — The  absolute  method,  while 
the  more  accurate  and  often  used  when  the  results  of  analysis  are  for 
the  purpose  of  determining  the  empirical  formula  of  a  compound,  is 
sometimes  replaced  by  the  Kjeldahl  or  wet  combustion  process.  In 
outline  the  method  is  as  follows:  The  organic  compound  is  decomposed 
and  oxidized  by  heating  for  some  time  in  about  30  cc.  of  pure  con- 


Q2O  APPENDIX 

centrated  sulphuric  acid.  A  catalyzer  and  other  reagents  for  special 
purposes  are  sometimes  added.  The  result, -however,  so  far  as  the 
nitrogen  is  concerned,  is  the  conversion  of  all  of  the  nitrogen  of  the 
organic  compound  into  ammonia  which,  in  the  presence  of  the  sul- 
phuric acid,  is  held  as  ammonium  sulphate.  After  the  completion  of  the 
acid  digestion  or  oxidation  the  liquid  is  cooled,  diluted  with  water 
and  a  strong  solution  of  sodium  hydroxide1,  more  than  sufficient  to 
neutralize  the  sulphuric  acid,  is  added.  The  flask  containing  the  liquid 
is  then  quickly  connected  with  a  condenser  and  the  free  ammonia  is 
distilled  into  a  standard  solution  of  hydrochloric  or  sulphuric  acid. 
After  the  distillation  has  been  continued  long  enough  to  drive  over  all  of 
the  ammonia,  the  standard  acid,  which  has  absorbed  the  liberated 
ammonia,  is  titrated  back  with  a  corresponding  standard  alkali.  This 
gives  us  the  amount  of  standard  acid  in  excess,  and  by  subtracting  this 
from  the  amount  of  standard  acid  originally  used,  we  obtain  the  amount 
of  standard  acid  neutralized  by  the  liberated  ammonia  and  from  this 
the  amount  of  ammonia  produced.  From  the  amount  of  ammonia 
produced  we  may  calculate  the  amount  of  nitrogen  in  the  original 
compound  or  we  may  calculate  the  amount  of  nitrogen  directly  from 
the  amount  of  standard  acid  neutralized.  The  Kjeldahl  method  has 
great  advantages  as  to  the  time  required  for  a  determination,  and  is 
accurate  enough  for  many  organic  nitrogen  determinations. 

Sulphur  by  the  Carius  Method. — Sulphur  in  organic  compounds  is 
commonly  determined  by  either  the  Carius  method  or  the  Liebig 
method.  The  Carius  method  consists  in  heating  a  small  amount  of 
the  compound  in  a  sealed  tube  with  pure  fuming  nitric  acid.  By  this 
treatment  the  sulphur  is  converted  into  sulphuric  acid,  which  is  then 
determined  in  the  usual  way  by  precipitation  as  barium  sulphate. 
The  tubes  in  which  the  heating  is  carried  out  are  known  as  Carius 
tubes  and  are  of  hard  glass,  one  end  only  being  sealed  at  the  beginning. 
As  long  as  the  tube  is  open~  the  compound  and  the  nitric  acid  are  kept 
separate,  one  being  introduced  into  the  tube  itself  and  the  other  into  a 
small  tube  or  vial  which  can  be  slipped  into  the  larger  tube.  After 
the  materials  have  been  placed  in  the  tube  the  open  end  is  sealed  by  fus- 
ion, the  tip  being  drawn  out  to  a  thick  walled  capillary.  Care  must 
be  taken  not  to  mix  the  contents  until  the  tube  is  sealed  and  cooled. 
When  cold,  the  tube  is  tipped  so  that  the  compound  and  acid  become 
thoroughly  mixed.  The  tube  is  then  placed  in  a  heavy  iron  oven, 


APPENDIX  Q2I 

known  as  a  bomb  oven,  and  heated  to  a  temperature  of  about  200°  - 
250°  for  some  hours.  The  temperature  and  the  length  of  time  of 
heating  vary  somewhat  with  the  compound.  After  cooling,  the  tube  is 
carefully  opened,  by  heating  the  capillary  tip,  and  then,  with  the  aid  of 
a  file,  the  tube  is  broken  in  two  near  the  capillary  end.  The  contents 
are  carefully  washed  out  into  a  beaker  and  the  determination  of  sulphur 
in  the  form  of  sulphuric  acid  is  then  completed  by  the  customary  pro- 
cedure, proper  precautions  being  observed  as  to  details. 

Sulphur  by  the  Liebig  Method.— By  the  Liebig  method  the  com- 
pound is  fused,  with  sodium  or  potassium  hydroxide,  in  a  silver  crucible. 
When  fused,  a  little  potassium  nitrate  is  added  as  an  oxidizing  agent. 
The  sulphur  of  the  organic  compound  is  thus  converted  into  sodium  or 
potassium  sulphate.  The  fused  mass  is  dissolved  in  water,  acidified  with 
nitric  acid,  and  the  sulphur  precipitated  as  barium  sulphate  by  the 
addition  of  barium  nitrate. 

Halogens  by  the  Carius  Method. — The  halogens,  chlorine,  bromine, 
iodine,  are  also  determined  by  the  Carius  method.  In  this  case,  crystal- 
line silver  nitrate,  nitric  acid  and  the  compound  under  examination  are  all 
introduced  into  the  Carius  tube.  The  nitric  acid  must  be  kept  separate 
from  the  compound  until  after  the  tube  is  sealed.  After  sealing  the 
tube  as  before,  the  contents  are  mixed  and  the  tube  heated  in  the  bomb 
oven.  The  halogen  of  the  organic  compound  is  converted  into  silver 
halide  which,  when  the  tube  is  opened,  is  carefully  washed  out,  filtered, 
and  weighed. 

Oxygen  by  Difference. — The  only  element,  usually  present,  which 
has  not  been  directly  determined  is  oxygen.  If  the  determinations 
made  do  not  total  to  approximately  100  per  cent  and  if  no  other 
element  is  present,  the  difference  between  100  per  cent  and  the  sum 
of  the  determinations  made  is  the  per  cent  of  oxygen  in  the  compound. 

EXAMPLE  OF  THE  CALCULATION  OF  THE  PERCENTAGE  COMPOSITION  AND  THE  EMPIRI- 
CAL FORMULA,  FROM  THE  DATA  OF  ANALYSIS 

A  compound  dry  and  with  no  water  of  crystallization  yielded  the  following  results: 
Carbon  and  Hydrogen  by  Combustion 

Wt.  compound  taken 0^5645  g. 

Wt.  CO2  obtained 0.8415  g. 

Wt.  H2O  obtained 0.4314  g. 

Carbon:  C  in  CC>2  =  27.27  per  cent;  0^2727  X  0.8415  g.  = 0.2295  g. 

o.  2295  g.  carbon  in  o.  5645  g.  compound  = 40-65  per  cent 

Hydrogen:  H  in  H2O  =  ii.n  per  cent;  o.im  X  0.4314  g.  = 0.0479  g. 

0.0479  g.  hydrogen  in  o.  5645  g.  compound  = 8.48  per  cent 


Q22  APPENDIX 

Nitrogen  by  the  Kjeldahl  Method 
Wt.  compound  taken o.  5215  g. 

—  HC1  in  absorption  flask 20. o  cc. 

N 

—  NaOH  for  back  titration 1 2 .  o  cc. 

10 

N                                               N 
-  HC1  equivalent  to  20.0  cc.  —  HC1 100.0  cc. 

10  2 

N 

—  HC1  neutralized  by  NH3  =  100. o  cc.  —  12 .o  cc.  = 88. o  cc. 

10 

N 

—  HC1;  i.o  cc.  is  equivalent  to  NHs,  0.0017  g-  °r  nitrogen  = 0.0014  g- 

Nitrogen  =  88.0  X  0.0014  g.  = o.  1232  g. 

o.  1232  g.  nitrogen  in  0.5215  g.  compound  =  .  .  . 23.62  per  cent 

Empirical  Formula. — The  calculation  of  the  empirical  formula  from  the  per- 
centage composition  is  as  follows: 


Atomic 
Element             Per  cent            weight 

Relative 
proportions, 
in  atoms 

Relative 
number 
of  atoms 

Empiri- 
formu 

c 

=    40 

65     + 

12 

=        3-4        •*- 

i. 

7       = 

2 

Co 

H 

=       8 

.48     * 

I 

=        8.5        * 

i. 

7       = 

5 

H5 

N 

=     23 

.62          -T- 

14 

=       i-7       +• 

i. 

7       = 

I 

N 

0 

=     27 

•25          4- 

16 

=        1.7       4- 

i 

•7       = 

I 

O 

(by  difference) 

The  percentage  amount  of  each  element  is  divided  by  the  atomic 
weight  of  the  element.  This  gives  the  relative  proportions  of  each 
element  in  atoms.  These  numbers  are  not,  however,  whole  numbers 
but,  by  dividing  each  by  the  smallest  one  found,  we  obtain  whole 
numbers  which  represent  the  relative  number  of  atoms  in  the  com- 
pound. The  formula  of  the  above  compound  is  thus  found  to  be  C2H5- 
ON  or  some  multiple  of  it.  Such  a  formula  is  known  as  an  empirical 
formula.  It  agrees  with  the  percentage  composition  of  the  compound, 
but  it  may  or  may  not  be  the  true  molecular  formula.  Any  multiple 
of  it  would  likewise  agree  with  the  percentage  composition.  The  only 
way  that  we  can  decide  on  the  true  molecular  formula  is  by  knowing 
the  molecular  weight  of  the  compound,  as  the  formula  C^H^ON  corre- 
sponds to  a  molecular  weight  of  59;  the  formula  C^ioOsN*,  to  a 
molecular  weight  of  118  and  the  formula  CeH^OsNa,  to  a  molecular 
weight  of  177. 


APPENDIX  923 

DETERMINATION  OF  THE  MOLECULAR  WEIGHT  OF  AN  ORGANIC 

COMPOUND 

The  molecular  weight  of  an  organic  compound  is  usually  ascertained 
by  one  of  three  determinations,  viz., 

(a)  The  vapor  density  of  the  compound, 

(b)  The  rise  in  the  boiling-point  of  a  solution  of  the  compound  above 
that  of  the  pure  solvent. 

(c)  The  lowering  of  the  freezing-point  of  a  solution  of  the  compound 
below  that  of  the  pure  solvent. 

Vapor  Density  by  the  Victor  Meyer  Method. — The  vapor  density 
of  a  compound  is  the  relative  weight  of  a  volume  of  it,  in  the  gaseous 
condition,  compared  with  the  weight  of  an  equal  volume  of  hydrogen. 
If  this  vapor  density  is  known,  it  is  possible  to  calculate  the  weight  of  a 
gram-molecular  volume  and  thus  the  molecular  weight.  The  method  of 
procedure  most  frequently  used  is  that  known  as  the  Victor  Meyer 
method,  which,  in  fact,  while  not  actually  weighing  a  definite  volume  of 
the  gas  determines  the  volume  of  air  displaced  by  a  definite  weight  of  the 
compound  after  it  is  converted  into  the  gaseous  condition.  The  appara- 
tus consists  of  a  long  tube  with  an  enlarged  lower  end  and  with  a  bent 
side  arm  through  which  the  displaced  air  may  be  driven  out  into  a 
eudiometer  tube.  The  compound  is  weighed  into  a  small  stoppered 
or  sealed  vial,  introduced  into  the  tube  and  then  vaporized  by  heat. 
The  heating  is  accomplished  by  placing  the  above  described  tube  in  a 
larger  glass  tube  or  outer  jacket  containing  some  liquid,  often  water, 
which,  when  boiled,  raises  the  temperature  of  the  inner  tube  above  the 
boiling-point  of  the  compound  under  examination.  The  heat  of  the 
outer  boiling  liquid  and  its  vapor  expands  the  liquid  compound  in  the 
vial,  forces  it  open  and  volatilizes  the  compound.  The  compound 
thus  converted  into  the  gaseous  condition  drives  out  of  the  upper  part 
of  the  inner  tube  a  volume  of  air  equal  to  the  volume  of  gas  produced. 
The  expelled  air  is  collected  in  a  eudiometer  tube  and  -accurately 
measured.  The  method  is  limited  to  those  substances,  usually  more  or 
less  volatile  liquids,  which  boil  at  temperatures  below  the  boiling-point 
of  water  or  some  other  liquid  that  is  applicable.  After  the  operation 
is  completed,  the  eudiometer  tube  is  carefully  transferred  to  a  tall 
cylinder  of  water  and  the  volume  of  air  contained  in  it  is  read  at 
atmospheric  temperature  and  pressure.  The  volume  of  air  in  cubic 


924  APPENDIX 

centimeters  must  then  be  corrected  to  standard  conditions  of  temperature 
and  pressure  (o°  and  760  mm.).  We  thus  have  a  volume  of  air  equal 
to  the  volume  of  gas  resulting  from  the  volatilization  of  a  known  weight 
of  compound.  In  other  words,  we  have  the  weight  of  a  definite  volume 
of  a  compound  in  the  gaseous  condition  and  from  this  we  calculate  either 
the  weight  of  a  liter  or  the  weight  of  a  gram-molecular  volume,  viz., 
22.4  liters.  This  gives  us  as  a  final  result  the  molecular  weight. 

EXAMPLE  OF  THE  CALCULATION  OF  THE  MOLECULAR  WEIGHT  OF  A  COMPOUND  FROM 
THE  DATA  OF  A  VAPOR  DENSITY  DETERMINATION 

A  compound  of  the  empirical  formula  CH&O  and  with  a  boiling-point  of  195° 
gives  the  following  data  as  the  result  of  a  determination  of  the  vapor  density  by  the 
Victor  Meyer  method. 

Wt.  Compound  taken o .  240  g. 

Volume  of  air  in  eudiometer  at  18°  and  750  mm 96 . 4  cc. 

Volmue  of  air  reduced  to  o°  and  760  mm.  (see  below) 87 . 3  cc. 

87 . 3  cc.  =  volume  of  gas  from o .  240  g. 

1000 .  o  cc.  gas  = 2 .  748  g. 

22400.0  cc.  (22.4  liters)  = 61.5  g. 

Molecular  weight  = 61.5 

A  compound  of  the  formula  CHsO  corresponds  to  a  molecular  weight  31. 
A  compound  of  the  formula  CzH-eOz  corresponds  to  a  molecular  weight  62.     There- 
fore the  molecular  formula  of  the  compound  determined  is  C2H6O2. 

The  reduction  of  a  volume  of  a  gas  represented  by  "F," 
measured  at  temperature  "/"  and  pressure  "P,"  to  the  volume  at 
standard  conditions,  viz.,  o°  and  760  mm.,  is  accomplished  by  the 
application  of  the  physical  equation: 

P  V 

Vo  =  760(1  +  al) 

As  the  air  was  measured  over  water,  the  pressure,  as  read  on  the  baro- 
meter, must  be  corrected  for  the  tension  of  water  vapor  "ze>"  at  the 
temperature  "t."  This  makes  the  equation: 

(P-w)V 

760  (i  +  a  /) 

Substituting  the  value  of  "w"  at  18°  which  is  15.33  mm.  and  the  values 
for  "P"  =  750  mm.;  "F"  =  96.4  cc.,  and  "a"  =  0.00366,  we  have 

v  -      (750  -  15-33)96.4 

760  (i  +  0.00366  X  18) 
FO  =  87.3  cc.  =  volume  of  air  at  o°  and  760  mm. 


APPENDIX 


925 


Rise  in  Boiling-Point  and  Lowering  of  Free  zing-Point. — The  other 
two  determinations,  which  enable  us  to  calculate  the  molecular  weight, 
are  based  on  the  fact,  that  when  a  non-ionized  substance  is  dissolved 
in  a  solvent,  the  boiling-point  of  the  solution  will  be  raised  above  that 
of  the  pure  solvent,  and  the  freezing-point  of  the  solution  will  be  lowered 
below  that  of  the  pure  solvent,  by  a  certain  amount,  depending  upon 
the  weight  of  the  solvent,  the  weight  of  the  substance  and  upon  its  molecu- 
lar weight.  Stated  in  another  way,  and  more  specifically:  a  gram- 
molecular  weight  of  any  non-ionized  compound  when  dissolved  in  1000 
grams  of  the  solvent  will  raise  the  boiling-point,  or  lower  the  freezing-point, 
of  the  solvent  a  constant  amount.  These  constants  are  termed  the 
molecular  rise  of  boiling-point  or  the  boiling-point  constant  and  the 
molecular  lowering  of  the  freezing-point  or  the  freezing-point  constant. 
The  values  of  these  constants  for  solvents  commonly  used  are: 

BOILING-POINT  CONSTANTS 


Solvent 

Gram-molecular  weight  of 
any  non-ionized  compound 
dissolved  in 

1000  g.  solvent 

100  g.  solvent 

Water 

•52° 
i.i5° 
1.67° 

2.11° 

2-53° 
2.61° 
2.67° 
3-°4° 
3.66° 

5-2° 

ii-5° 
16.7° 

21.1° 

25.3° 
26.1° 
26.7° 
30.4° 

36.6° 

Alcohol  
Acetone  
Ether 

Acetic  acid  

Ethyl  acetate  
Benzene  
Phenol  
Chloroform 

FREEZING-POINT  CONSTANTS 


Solvent 


Gram-molecular  weight  of 

any  non-ionized  compound 

dissolved  in 


1000  g.  solvent   loog.  solvent 


Water                         i  .  86° 

18.6° 

Acetic  acid  3-9° 
Benzene.  .  .                                                                                                    ^  •  oo 

39-o° 
so.o° 

Q26  APPENDIX 

The  problem,  therefore,  is  to  have  apparatus  enabling  us  to  determine 
accurately  the  rise  in  the  boiling-point  and  the  lowering  of  the  freezing- 
point  when  a  known  weight  of  a  compound  is  dissolved  in  a  known 
weight  of  the  solvent.  From  this  we  can  calculate  the  weight  of 
compound  necessary  to  produce  the  molecular  rise  or  lowering  and 
this  amount  will  be  the  molecular  weight  of  the  compound.  The 
pieces  of  apparatus  used  in  these  determinations  and  the  procedure  in 
carrying  out  a  determination  are  complicated,  and  a  description  in 
more  detail  in  this  book  seems  out  of  place.  Great  care  must  be 
observed  in  carrying  out  a  determination  and  various  corrections  must 
be  applied.  The  result  obtained,  so  far  as  its  application  to  organic 
chemistry  is  concerned,  is  that  we  obtain,  in  the  end,  the  molecular 
weight  of  the  compound  in  question  and  this  is  essential  in  order  to 
use  the  data  of  analysis  for  the  purpose  of  determining  the  molecular 
formula  of  a  compound. 

EXAMPLE  OF  THE  CALCULATION  OF  THE  MOLECULAR  WEIGHT  OF  A  COMPOUND  FROM 
THE  DATA  OF  DETERMINATIONS  OF  RISE  IN  BOILING-POINT  AND 

LOWERING  OF  FREEZING-POINT 

The  compound  used  in  the  example  of  the  analysis  for  carbon,  hydrogen,  nitrogen 
and  oxygen,  and  which  gave  results  from  which  the  empirical  formula  was  calculated 
to  be  C2HsON,  gave  the  following  results  for  the  rise  in  boiling-point  of  ether. 

Wt.  compound  taken o .  350  g. 

Wt.  solvent  (ether) 52 . 850  g. 

Rise  in  boiling  point  observed o.  25° 

The  physical  equation  for  calculating  the  molecular  weight  from  the 
rise  in  boiling-point  is  as  follows: 

100  w 


M  =  C 


RW 


In  this  equation     "M  "  =  the  molecular  weight 

"C"    =  the  boiling-point  constant  for  100  g.  solvent 
"  w"    =  the  weight  of  compound  in  grams 
"W"  =  the  weight  of  solvent  in  grams 
"R"   =  the  rise  of  boiling-point  in  degrees. 

From  our  data,  then,  we  have  as  follows  : 

M  = 


0.25  X  52-85 
=  55-87 


APPENDIX  927 

The  molecular  weight  of  55.87  corresponds  more  nearly  to  the  molecular 
formula  C4H&ON,  with  calculated  molecular  weight  of  59,  than  to  the 
formula  C4Hi0O2N2  or  C6H15O3N3  with  calculated  molecular  weights 
of  118  and  177.  Very  close  agreement  between  the  calculated  and 
determined  values  is  not  usual  in  practice,  nor  is  it  necessary,  as  it  is 
only  required  to  select  between  molecular  weights  that  are  quite 
different  in  value. 

The  same  compound  was  used  for  the  determination  of  the  lowering 
of  the  freezing-point  of  water.     The  data  obtained  are  as  follows: 

Wt.  substance,  0.525  g. 

Wt.  solvent  (water),  55-32Q  g. 

Lowering  of  freezing-point,          0.30° 

The  physical  equation  for  deriving  the  molecular  weight  from  the 
freezing-point  lowering  is  analogous  to  the  one  which  applies  to  the  rise 
in  boiling-point.  It  is  as  follows: 

100  W 

~LW 

"L"  =  observed  lowering  of  freezing-point 

"C"  =  freezing-point  constant  for  100  g.  solvent. 

Substituting  in  this  equation  the  values  obtained  in  the  determination 
we  have: 

M  =  I8.6  I00 


0.3  X  55-32 
M  =  58.8 

The  molecular  weight  is  therefore  58.8,  according  to  the  determina- 
tion, and  the  formula  of  the  compound  must  be  C2H5ON  with  the 
theoretical  molecular  weight  of  59. 


INDEX 


Abbe-Zeiss,  211 
Abderhalden,  393 
Acetal,  117 
Acetaldehyde,  119,  120,  252 

ethyl  mercaptal,  197 
Acet-aldoxime,  125 
Acetamide,  140,  146,  148,  556 

Tautomerism  of,  146 
Acetanilide,  556 
Acetic  acid,  131,  135 

anhydride,  139 

fermentation,  135 

Glacial,  136 
Acet-ketoxime,  125 
Acet-methyl  anilide,  551,  557 
Aceto  acetic  acid,  254 

Acid  hydrolysis  of,  257 

Alkyl  derivatives  of,  257 

Constitution  of,  256 

Ketone  hydrolysis  of,  256 

Sodium  salt  of,  257 

Tautomerism  of,  256 
Aceto  acetic  ester  synthesis,  258 

of  di-acetyl,  262 

of  glutaric  acid,  286 
Acetone,  119,  122,  124 

ethyl  mercaptol,  197 
Acetophenone,  647,  657 
Acet-toluides,  544 
Acetyl,  138 

acetone,  263 

chloride,  137 

salicylic  acid,  719 
Acetylation,  138,  318,  683 
Acetylene,  160,  161,  162 

carboxylic  acid,  181 

series,  159 
59 


Achroo-dextrin,  362,  380 
Acid  amides,  144 

Dehydration  of,  147 

Hydrolysis  of,  147 

Properties  of,  145 

Reactions  of,  145,  146 

Relation  of,  148 
Acid  anhydrides,  139 

Reactions  of,  139 
Acid  chlorides,  137 

Reactions  of,  138 
Acid  hydrolysis,  258 
Acid  nitriles,  66,  69 

from  sulphonic  acids,  521 
Acid  potassium  oxalate,  271 
Acid  potassium  tartrate,  310 
Acid  yellow,  573 
Acids,  125 

Action  of  metals  on,  126 

Action  of  PCU  on,  126 

Alpha-,  beta-,  and  gamma-,  233 

Aromatic,  669 

as  oxidized  hydrocarbons,  289-290 

Composition  of,  126 

Constitution  of,  126 

Derivatives  of,  137 

Halogenation  of,  230 

Homologous  series  of,  130,  131 

Isomerism  of,  130 

Names  of,  130 

Occurrence  of,  134 

Preparation  of,  130 

Properties  of,  132 

Reactions  of,  133 

relation  to  hydrocarbons,  1 29 

Substituted,  229,  231 

Unsaturated,  170 
Aconitic  acid,  312 
Acree,  762 


929 


930 


INDEX 


Acridon,  667 
Acrolein,  158 

di-bromide,  341 
Acrose,  Alpha,  341,  352,  363 
Acrylic  acid,  172,  242,  245,  697 
Acrylic  aldehyde,  168 
A-cyclic  compounds,  20 
Acyl  radical,  138 
Adenine,  450,  901,  903 
Addition,  153,  156 
Adipic  acid,  288 
Adipo-cellulose,  367 
Agar-agar,  380 
Alanine,  389 

anhydride,  400 
Alanyl  alanine,  400 
Alanyl  glycine,  401 
Albumin  in  urine,  447 
Albuminates,  406 
Albuminoids,  398 
Albumins,  398 
Alcohol,  95 

Absolute,  98 

acids,  Aromatic,  728 

Denatured,  100 

Industrial,  99 

lodoform  test  for,  186 

of  crystallization,  82 

Oxidation  of,  114 

Properties  and  uses  of,  98 

reaction  with  HBr,  81 

reaction  with  PCls,  80 

reaction  with  sodium,  79 

Synthesis  of,  81 

tax,  99 

Alcoholic  beverages,  98 
Alcoholic  fermentation,  95,  360 
Alcohols,  78 

Aromatic,  607,  641 

Derivatives  of,  102 

from  alkyl  halides,  81 

Homologous  series  of,  84 

Isomerism  of,  84 

Names  of,  84,  87 

Oxidation  products  of,  112 

Polymerization  of,  117 


Alcohols,  Preparation  of,  92 

Primary,  121,  122 

Properties  of,  92 

Reducing  action  of,  118 

Secondary,  121,  123 

Table  of,  85,  86 

Tertiary,  123 

Unsaturated,  166 
Aldehyde,  112 

acids,  251 

alcohols,  228 

ammonia,  116 

group,  114 

hydrogen  cyanide,  116,  226 

sodium  acid  sulphite,  116 
Aldehydes,  112 

Addition  products  of,  116 

Aromatic,  647,  654 

Constitution  of,  112 

Hydroxy,  228 

Nomenclature  of,  118 

relation  to  ketones,  123 

Substituted,  226 

Table  of,  119 

Unsaturated,  168 
Aldehydrol,  347 
Aldo-hexoses,  340 
Aldol,  117,  169,  229 

condensation,  116,  169,  229,  337 
Aldose,  conversion  into  ketose,  328 
Ali-cyclic  compounds,  460 
Aliphatic  series,  Resume  of,  453 
Alizarin,  747,  800,  805 

Commercial  synthesis  of,  803 

Constitution  of,  802 

dyes,  806 

reduction  to  anthracene,  80 1 
"  Synthesis  of,  801 
Alkaloids,  450,  884 

Coca,  894 

Di-heterocyclic,  892 

Purine,  900 

Pyridine,  885 

Quinoline,  886 

Solanacese,  892 
Alkyl,  21 


INDEX 


931 


Alkyl,  amines,  54 

Homologous  series  of,  62 
Synthesis  of,  54 
anilines,  546,  553 
cyanides,  66,  411 
halides,  45 

Isomerism  of,  45 
Names  of,  49 
Preparation  of,  49 
Properties  of,  51 
Synthetic  use  of,  49 
Table  of,  46 
Uses  of,  51 
iso-cyanides,  411 
magnesium  halides,  77 
phosphines,  65 
phosphonium  iodides,  65 
ureas,  436 
zinc  halides,  76 
Allantoin,  439,  443 
Allo-cinnamic  acid,  699 
Alloxan,  439,  443 
Allyl,  165 

alcohol,  1 66 
cyanides,  165 
halides,  165 

iso-thio-cyanate,  165,  421 
sulphide,  167 
thio-cyanate,  165,  420 
thio-ether,  167 
Allylene,  167,  489 
Almond  oil,  210,  211,  215,  216 
Aluminium  carbide,  6,  44 
Alypine,  897 
Amatol,  534 
Amidol,  633 
Amine  salts,  55 
Amines,  54 

and  nitrous  acid,  60,  546 
Aromatic,  539 
Basic  character  of,  55 
Isomerism  of,  61 
Primary,  57,  60,  546 

Test  for,  70 
Secondary,  57,  61,  546 
Tertiary,  57,  6 1,  546 


Amino,  55 

acids,  382,  703 

Anhydrides  of,  386 
Aromatic,  705 
from  proteins,  384,  388 
Salts  of,  384 
Synthesis  of,  382 
alcohols,  225 
alkanes,  54 

azo  benzene,  567,  569,  573 
azo  compounds,  569,  570 
azo  toluenes,  571 
benzene,  530,  536,  539 
sulphonic  acid,  560 
relation  to  dyes,  562 
benzoic  acid,  706,  871 
benzophenone,  666 
benzoyl  formic  acid,  868 
butyric  acid,  390 

Gamma,  456 
cinnamic  acid,  710 
compounds,  54 
di-methyl  aniline,  552,  562 
glutaric  acid,  288,  391 
ketones,  666 
naphthalene,  770 
naphthalenes,  779 
naphthol  sulphonic  acid,  786 
phenol,  Para,  564,  631 
phenols,  631 

Derivatives  of,  633 
Dyes  from,  635 
phenyl  propiolic  acid,  711 
purine,  901 
valeric  acid,  390 

Delta,  456" 
Ammonal,  534 

Ammonia  derivatives,  54,  539 
Ammoniacal  gas  liquor,  496 
Ammonio-zinc  chloride,  612,  632,  779, 

783 

Ammonium  carbamate,  430 
Ammonium  cyanate,  418,  429 
Ammonium  hydrazoate,  64 
Ammonium  thio-cyanate,  420 
Amygdalin,  654,  729 


932 


INDEX 


Amyl  alcohol,  Active,  89 

Amyl  alcohols,  101 

Amyl  nitrite,  587 

Amyloid,  368 

Analysis  of  organic  compounds,  917 

Anesthesine,  898 

Anesthetics,  Synthetic,  895 

Anethole,  623,  663,  664,  720,  841,  842 

Angelic  acid,  178 

Anhydrides,  139 

Inner,  234 

of  liydroxy  acids,  241 
Anilides,  543,  555 
Aniline,  497,  530,  536,  539,  871 

and  nitrous  acid,  542,  586 

dyes,  541,  744 

History  of,  539 

Preparation  of,  540 

Salts  of,  555 

yellow,  573 

Anilines,  Substituted,  546,  557 
Anilino  acetic  acid,  561 
Anilino  acids,  561 

Anis  aldehyde,  66 1,  664,  720,  841,  842 
Anisic  acid,  720 
Anisole,  612,  621,  720 
Anol,  623,  663 
Anschiitz,  793 
Anthracene,  496,  499,  765,  792 

and  derivatives,  792 

Constitution  of,  794,  798 
'  from  benzyl  bromide,  794 

from  benzyl  toluene,  793 

from  phenyl  ortho-tolyl  ketone,  794 

from  tetra-brom  ethane,  793 

Isomerism  of  derivatives  of,  800 

oil,  497 

Synthesis  of,  793 
Anthranil,  707 
Anthranilic  acid,  705,  706,  871 

from  naphthalene,  708,  880 

from     phenyl     glycine     ortho-car- 
boxylic  acid,  710 

relation  to  indigo,  706 

Synthesis  of,  708 
Anthranilo  acetic  acid,  710 


Anthraquinone,  795 

Constitution  of,  798 

from  phthalic  acid,  795 

sulphonic  acid,  803 

Synthesis  of,  795 
Antifebrin,  556 
Anti  formula,  592 
Antipyrine,  856 
Arabinose,  218,  339 
Arabitol,  218,  33*9 

Arachidic  acid,  131,  137,  180,  204,  216 
Arachidin,  208 
Arbutin,  618 
Arginine,  391 
Armstrong,  349 

and  Baeyer,  475 
Aromatic  acids,  669 

by  Gattermann  synthesis,  674 

by  Grignard  reaction,  677,  680 

by  Kekule  synthesis,  675 

by  Wurtz  synthesis,  675 

from  amides,  676 

from  cyanides,  675 

from  diazo  compounds,  677 

from  hydrocarbons,  674 

from  malonic  ester,  679 

from  sulphonic  acids,  675 

Ring-carboxy,  673 

Substituted,  701 

Synthesis  of,  669 
Aromatic  alcohols,  607,  641 

by  Grignard  reaction,  642 
Aromatic  aldehydes,  647 

and  ketones,  647 

Reactions  of,  650 

Substituted,  658 

Synthesis  of,  648 
Aromatic  amines,  539 

Derivatives  of,  545 

Nitrous  acid  on,  541 

Reactions  of,  541  , 

Aromatic  compounds,  466 
Aromatic  glycols,  645 
Aromatic  ketones,  657 
Arsenic  compounds,  64 
Arsines,  65 


INDEX 


933 


Aryl  amines,  Reactions  of,  549 
Aryl  anilines,  546 
Asparagine,  391 
Aspartic  acid,  391 
Aspirin,  719 
Asymmetric  carbon,  90 
Atropic  acid,  699 
Atropine,  699,  892 
Auramine,  667,  734 
Aurines,  748 
Azo,  568 

benzene,  537,  563,  566 

compounds,  567,  568,  569 

dyes,  576 

from  naphthalene,  786,  789 

toluene,  567 
Azoxy  benzene,  537,  563,  565 

Rearrangement  of,  566 


H 


Baeyer,  442,  762,  801 

and  Caro,  80 1 

and  Drewsen,  862,  879 
Ballistite,  378 
Bamberger,  462,  772 
Barbier,  77 

Barbituric  acid,  438,  443,  457 
Beckmann  rearrangement,  654,  658,  685 
Bees'  wax,  216 

Behrend  and  Roosen,  442,  445 
Beilstein,  31,  36 
Benedict,  332 
Benzal  chloride,  510 
Benzaldehyde,  647,  654,  841,  842 
Benzaldoxime,  651,  652 

Syn  and  anti,  652 
Benzamide,  68%. 
Benzamine,  539 
Benzanilide,  557,  658,  685 

by  Beckmann  rearrangement,  685 
Benzene,  42,  458,  469,  476,  496,  498 

azo  toluene,  567 

compounds,  458 

Constitution  of,  466 

derivatives,  458,  502 


Benzene,  diazo  hydroxide,  591 
diazo  sulphonic  acid,  593 
diazonium  chloride,  568,  586,  587, 

590 

Griess  formula  for,  588 
Kekule  formula  for,  589 

diazonium  hydroxide,  590 

diazonium  potassium  sulphite,  593 

di-sulphonic  acid,  516 

from  acetylene,  478 

from  benzoic  acid,  682 

Halogen  products  of,  470,  502,  507 

Hexa-carboxy,  695 

hexa-chloride,  504 

Hexagon  formula  for,  469,  471,  476 

Homologues  of,  470,  476 

Hydroxyl  products  of,  470 

Isomerism  of  derivatives  of,  471 

Kekule  formula  for,  474 

Nitric  acid  derivatives  of,  470,  528 

Properties  of,  469 

series,  458,  466 

Substitution  products  of,  470 

sulphinic  acid,  523,  525 

sulphon  amide,  519 

sulphon  chloride,  519 

sulphonic  acids,  470,  515 

Synthesis  of,  477 

Theories  of  formation  of,  501 
Benzidine,  578,  732,  787 

dyes,  579,  787 
Benzil,  763 

di-oximes,  764 
Benzine,  40,  458 
Benzoic  acid,  511,  521,  671,  673,  680 

Esters  of,  682 

Reduction  of,  682 

Synthesis  of,  68 1 
Benzoic  anhydride,  683 
Benzoic  nitrile,  521,  599,  652 
Benzoic  sulphinid,  712 
Benzoin,  763 
Benzophenone,  657,  734 

from  benzoic  acid,  682 
Benzopurpurin,  788 
Benzoquinone,  636,  638,  795 


934 


INDEX 


Benzo  tri-chloride,  510 
Benzoyl,  683 

amino  acetic  acid,  684 

amino  compounds,  683 

brom  benzoic  acid,  796 

chloride,  683 

ecgonine,  897 

glycine,  388,  686 

phenyl  urea,  685 
Benzoylation,  683 
Benzyl,  644 

acetate,  644 

alcohol,  641,  644 

amine,  544 

bromide,  794 

chloride,  510 

hydroxyl  amine,  565 

methyl  ether,  644 

toluene,  793 
Bernthsen,  762 
Berthelot,  6,  204,  501 
Berthelot's  synthesis,  6 
Berzelius,  9,  23,  235 
Betaine,  388,  908 
Betol,  719,  784 
Bioses,  336 
Bismarck  brown,  575 
Biuret,  405,  434 

reaction,  405 
Bivalent  carbon,  71,  419 
Bloomstrand-Strecker-Erlenmeyer     for- 
mula, 590 
Boiling-point,  915 

constants,  925 

Determination  of,  916 

rise,  Determination  of,  925 
Books  of  reference,  910 
Bourdeaux  B,  789 
Borneo  camphor,  825,  835 
Borneol,  823,  835,  838,  842 
Bornyl  chloride,  838 
Bornylene,  823,  835 
Bouchardat,  846 
Brom  anthraquinone,  796 
Brom  benzoic  acid,  704 
Brom  ethane,  51 


Brom  phthalic  anhydride,  796 

Bromoform,  186 

Brucine,  889 

Bucher,  423 

Buchner,  96 

Bunsen,  66 

Butanal,  119 

Butan-di-oic  acid,  278 

Butane,  18,  28 

Synthesis  of,  20,  24 

Methyl,  33 

Di-methyl,  34 
Butenal,  169 

Butenes,  Isomerism  of,  157 
Butenoic  acids,  173 
Butlerow,  340 
Butter  fat,  208,  210,  211,  213,  215,  216 

Composition  of,  217 
Butter  yellow,  573 

Butyl  alcohol,  by  Grignard  reaction,  78 
Butyl  iodide,  Primary,  48 
Butyl  iodide,  Secondary,  48 
Butyl  iodide,  Tertiary,  48 
Butylene,  157 

Butyric  acid,  131,  136,  204,  209,  216,  217 
Butyrin,  207,  208,  213 
Butyro  lactone,  243,  849 
Butyro-refractometer,  211 


Cacodyl,  66 

Cadaverine,  193,  194,  856,  905 
Caffeine,  448,  901,  903 
Caffe-tannic  acid,  724 
Cagniard  de  Latour,  95 
Cain  and  Thorpe,  746 
Calcium  carbide,  44,  164 
Calcium  cyan  amide,  422 
Camphane,  822 
Camphene,  823,  842 
Camphor,  491,  616,  811,  814,  835,  838, 
841,  842 

Borneo,  825 

Constitution  of,  835 

Natural,  838 


INDEX 


935 


Camphor,  Synthesis  of,  823,  837 
Camphoric  acid,  Kompa's  synthesis  of, 

835 

Camphors,  825 
Cane  sugar,  353 

Analysis  of,  358 

Diffusion  process  for,  355 

Extraction  of,  355 

History  and  statistics  of,  357 

Industrial  processes  for,  354 

Sources  of,  354 
Caoutchouc,  811,  814,  815,  843 

Harries  formula  for,  848 

Properties  of,  843 

Synthesis  of,  845 

Capric  acid,  131,  137,  204,  209,  216,  217 
Caprin,  208 
Caprine,  390 

Caproic  acid,  131,  204,  209,  216,  217 
Caproin,  208 

Caprylic  acid,  131,  204,  209,  216,  217 
Caprylin,  208 
Carane,  822 
Carbamic  acid,  430 
Carbamide,  429 
Carbazole,  792 
Carbinol  base,  738,  740 
Carbo-cyclic  compounds,  458,  460 
Carbohydrates,  316 

Acetylation  of,  318 

Aldehyde  reactions  of,  319 

and  Fehling's  solution,  332 

and  phenyl  hydrazine,  326 

Classification  of,  333 

Composition  of,  316 

Constitution  of,  316,  323 

Conversion  of,  325 

Decreasing  carbon  content  of,  329 

Derivatives  of,  325 

Esterification  of,  318 

Fermentation  of,  331 

Increasing  carbon  content  of,  329 

Number  of  hydroxyls  in,  318 

Oxidation  of,  325 

Position  of  aldehyde  group  in,  322 

Position  of  ketone  group  in,  323 


Carbohydrates,  Reactions  of,  331 

Reagent  for,  581 

Reduction  of,  321 

Synthesis  of,  320 

Table  of,  381 
Carbolic  acid,  496,  613 
Carbon,  2 

Bivalent,  419 

by  combustion,  918 

Tetra-valence  of,  10,  473 

Tri-valent,  762 
Carbon  dioxide,  425 

Reduction  of,  267 
Carbon  tetra-chloride,  9,  187 
Carbonates,  425 
Carbonic  acid,  425,  428 
Carbonyl  chloride,  187,  426 
Carbonyl  group,  114,  121 
Carbostyril,  863 
Carboxy  cinnamic  acids,  673 
Carboxyl,  127 

in  the  ring,  671 

in  the  side-chain,  672 

Influence  of,  702 
Carbylamines,  69 
Carius  method  for  halogens,  920 
Carius  method  for  sulphur,  920 
Carnauba  wax,  216 
Caro,  494,  746 

and  Frank,  422 
Carvacrol,  615,  827,  832 
Carvene,  820 
Carvo-menthol,  826 
Carvo-menthone,  826 
Carvone,  829,  831,  832,  841,  842 
Casein,  393 
Caseinogen,  396 
Castor  oil,  216 
Catechu-tannic  acid,  724 
Cellobiose,  368 
Cellulase,  362 
Celluloid,  376 
Cellulose,  361,  366 

Acetates  of,  374 

Compound,  366 

Constitution  of,  368 


936 


INDEX 


Cellulose,  explosives,  376 

Formula  for,  370 

Hydrates  of,  374 

Industrial  uses  of,  369 

Nitration  of,  377 

Nitric  acid  esters  of,  375 

Normal,  366 

Properties  of,  367 
Centric  formula,  475 
Cerotic  acid,  216 
Cetyl  alcohol,  93 
Chardonnet,  373 
Chavicol,  623,  663 
Chevreul,  180,  204 
Chinitol,  814 
Chlor  acetic  acids,  234 
Chlor  benzoic  acids,  511,  704 
Chlor  ethane,  51 
Chlor  formic  acid,  234 
Chlor  methanes,  8,  10,  52,  182 
Chlor  naphthalenes,  771 
Chlor  picrin,  220 
Chlor  propenes,  164 
Chlor  pyridine,  856 
Chlor  toluenes,  510,  512 
Chlor  tri-methyl  benzenes,  513 
Chlor  xylenes,  513 
Chloral,  226 

hydrate,  227,  252,  297 
Chloranil,  639 
Chloranilic  acid,  639 
Chloroform,  8,  183 

Reactions  of,  184 
Chlorophyll,  363 
Choline,  906 
Chromophore,  740 
Chrysoidine,  574 
Cinchona  alkaloids,  887 

Action  of,  889 
Cinchona  bark,  888 
Cinchonidine,  888 
Cinchonine,  887 
Cinchoninic  acid,  864,  887 
Cineol,  841,  842 
Cinnamic  acids,  645,  672,  697,  698 

Carboxy,  672 


Cinnamic  alcohol,  645 

Cinnamic  aldehyde,  656,  699,  841,  842, 

86 1 

Cinnamyl  acetate,  842 
Cinnamyl  cocaine,  895 
Citra-conic  acid,  293,  315 
Citral,  816,  841,  842 
Citrene,  815,  819 
Citric  acid,  313 

from  aceto  acetic  ester,  314 

from  glycerol,  313 

Salts  of,  315 
Citronellal,  841 
Citronellol,  841,  842 
Claisen,  254 

Claus  diagonal  formula,  475 
Cleaning  oil,  40 
Coagulated  proteins,  399 
Coal,  Distillation  of,  494 
Coal  gas,  4,  494 
Coal  tar,  467,  477,  494,  496 

Distillation  of,  497 

dyes,  541,  747 

industry,  500 

Yield  of  products  from,  500 
Coca  alkaloids,  894 
Cocaine,  699,  894 

Alpha,  896 
Cochineal,  747 

Cocoa  butter,  208,  210,  211,  215,  216 
Cocoanut  oil,  208,  210,  211,  215,  216 
Codeine,  890 
Cod-liver  oil,  210,  216 
Cohen,  293 
Cohnheim,  393 
Coke,  43,  495 

Collidine,  Synthesis  of,  859 
Collidines,  858,  860 
Collodion,  203^376 
Cologne  spirits,  98 
Colophony,  840 
Columbian  spirits,  94 
Combustion  analysis,  918 
Condensation,  116,  169,  229,  337 
Condensed     hetero-cyclic     compounds, 
860 


INDEX 


937 


Condensed  ring  compounds,  765,  793 

Congo  red,  787 

Coniferin,  646 

Coniferyl  alcohol,  646,  663,  664 

Conine,  858,  885 

Synthesis  of,  885 
Constitution,  10 
Constitutional  formula,  12 
Cordite,  378 
Cotton,  370 

Mercerized,  372 

Cotton-seed  oil,  208,  210,  211,  215,  216 
Coumaric  acid,  726 
Coumarin,  727 
Coumarinic  acid,  726 
Coumarone,  865 
Cream  of  tartar,  310 
Creatine,  441,  446,  903 
Creatinine,  441,  446,  903 
Cresols,  497,  614,  641 
Crotonic  acid,  173,  174,  177,  204,  292 

Cis  form  of,  177 

from  ace  to  acetic  ester,  260 

Isomerism  of,  176 

Synthesis  of,  175 
Crotonic  aldehyde,  169 
Crystalline,  539 
Crystallization,  914 
Cumene,  491 
Cuminic  aldehyde,  656 
Curtius,  64 
Cyan-amide,  221,  421 
Cyanates,  408 
Cyanic  acid,  416 
Cyanides,  66,  408,  410 

from  atmospheric  nitrogen,  422 
Cyanogen,  68,  193,  408 

alcohols,  225 

chloride,  421 

compounds,  Tautomerism  of,  413 

Hydrolysis  of,  265 

radical,  68 
Cyano  methane,  68 
Cyano  methyl  anthranilic  acid,  88 1 
Cyanol,  539 
Cyanuric  acid,  418 


Cyclic  terpenes,  816 
Cyclic  ureids,  438 
Cyclo-butane,  461 

-hexan-di-ol,  813 

-hexane,  461,  469,  504,  811,  813 

-hexanols,  813 

-paraffins,  462 

-pentane,  461 

-propane,  173,  460 

-propene,  462 

-propine,  462 

Cymene,  476,  492,  817,  821 
Cystine,  389 

D 

Been,  320 

Denatured  alcohol,  100 
Desmotropism,  525 
Dessaignes,  686 
Dextrin,  361,  379 
Dextrose,  351 
Di-acetanilide,  557 
-acetic  acid,  279 
-acetyl,  262 
-acetyl  morphine,  892 
-aldehydes,  261 
-amide,  64,  579 
-amine,  64 

-amino  acetic  acid,  389 
azo  benzene,  574 
benzene,  561 
butane,  193 
di-phenyl,  579,  732 
pentane,  193 
anilides,  557 
-anisidine,  732 
-benzyl,  762 
-brom  ethane,  Symmetrical,  154 

Unsymmetrical,  153 
-chlor  acetic  acid,  234 
benzene,  505 

ethane,  Isomerism  of,  53,  188 
Symmetrical,  53,  188 
Unsymmetrical,  53, 

113,  188 
hydrine,  202 


938 


INDEX 


Di-chlor  methane,  8,  52 
toluenes,  510 
-cyano  methane,  273 
-cyclic  terpenes,  821 
-enes,  162 
-ethyl,  28 

carbonate,  427 

di-sulphone  di-methyl  methane, 

198 

malonate,  275 
oxalate,  271 
sulphate,  515 
sulphone,  197 
thio-ether,  197 
-ethylenes,  162 
-gallic  acid,  723 
-glycolic  acid,  240 
anhydride,  245 
-hydro  benzene,  812 
carveol,  829 
carvone,  829 
collidine,  859 
cymene,  817 
terrephthalic  acid,  694 
-hydroxy  acetone,  228,  320,  337 
alcohols,  195 
anthraquinone,  801 
benzenes,  616 
malonic  acid,  296 
succinic  acid,  301 
-ketones,  261 
-keto  piperizines,  386 
-methyl,  17 

amino  azo  benzene,  567,  573 

ammonium  iodide,  57 

aniline,  550,  552,  747 

benzenes,  483 

glutaric  acid,  835 

hydrazine,  64 

ketone,  124 

octa  di-ene,  815 

oxamic  acid,  273 

oxamide,  273 

phenyl  pyrrazolone,  856 

pyridines,  858 

succinic  acid,  284 


Di-methyl     tri-methylene     di-bromide, 

846 

-methyl  xanthine,  901 
-nitro  benzene,  530 
di-phenyl,  731 
di-phenyl  di-acetylene,   873, 

878 

-oxindole,  866 
-oxy  purine,  900 
-pentene,  819,  842,  846 
-peptides,  386 
-phenic  acid,  733,  809 
-phenyl,  730 
amine,  546,  555 
di-acetylene,  873 
iodonium  hydroxide,  508 
ketone,  657 
methane,  657,  733 
Synthesis  of,  733 
phthalide,  751 
thio-urea,  543 
-propargyl,  163,  167,  467 
-propyl,  30 
-saccharoses,  334,  353 
-sulphonic  acids,  Reactions  of,  522 
-thio  acetal,  197 
Dialuric  acid,  438,  443 
Diastase,  95,  360,  362 
Diazo  acids,  711 
Diazo  amino  compounds,  570 
Diazo  benzene,  542,  547,  563,  586 
Diazo  compounds,  568,  585 
and  alcohols,  597 
and  cyanides,  599 
and  water,  597 
Constitution  of,  587 
Griess  formula  for,  588 
Kekul6  formula  for,  589 
Oxidation  of,  596 
Reactions  of,  595,  600 
Reduction  of,  595 
Tautomerism  of,  591 
Diazo  esters,  594 
Diazo  reaction,  569 
Diazo  reactions,  Table  of,  600-603 
Diazonium  compounds,  Formula  for,  590 


INDEX 


939 


Diazotates,  591 

Hantzsch  formula,  592 

Isomerism  of,  591 
Diazotization,  586 
Dibasic  acids,  288 

Saturated,  264 

Unsaturated,  289 
Diffusion  process,  355 
Dionine,  892 
Dis-azo  compounds,  572 
Divalent  mercaptans,  197 
Double  bonds,  155 
Dulcitol,  219,  339 
Dumas,  9,  235 

method  for  nitrogen,  919 
Durene,  491 
Dyes,  744 

Auramine,  734 

Carbinol  base  of,  740 

Coal  tar,  747 

Colored  dye  salt  of,  741 

Colorless  hydrate  salt  of,  741 

History  of,  744 

Leuco  base  of,  740 

Phthalein,  750 

Quinoid  constitution  of,  740 

Substantive,  788 

Synthetic,  746 

Tri-phenyl  methane,  736 
Dynamite,  202,  379 


Ecgonine,  894 
Edestin,  394 
Egg  albumin,  392,  394 
Eikonogen,  786 
Elaidic  acid,  178,  204 

from  oleic  acid,  179 
Emulsin,  655 
Enantiomorphs,  91,  307 
Engler,  43 
Enol  formula,  256 

Enzymatic  hydrolysis  of  proteins,  404 
Enzyme  theory  of  fermentation,  96 
Eosine,  761 
Epi-chlor  hydrines,  224 


Erepsin,  404 
Ergot  base,  906 
Erlenmeyer,  769 
Erythrin,  218 
Erythrite,  218 
Erythritol,  218,  337 
Erythro-dextrin,  362,  379 
Erythrose,  337 
Essential  oils,  66 1,  814,  840 

Table  of,  842 
Esterification,  140 
Esters,  102,  140 

Isomerism  of,  142 

Names  of,  142 

Occurrence  of,  143,  841 

Preparation  of,  143 

Properties  of,  105,  143 
Estragole,  623,  663,  842 
Ethanal,  119,  120 
Ethane,  15,  463 

Oxidation  products  of,  266 

Synthesis  of,  15 
Ethanoic  acid,  131,  135 
Ethan-ol,  84,  95 
Ethene,  151,  157,  158 

series,  157 
Ethenol,  166 
Ether,  108 

an  anhydride,  no 
Ethereal  oils,  814,  840 
Ethereal  salts,  102 
Ethers,  105 

Chemical  properties  of,  108 

Isomerism  of,  106 

Names  of,  106 

Synthesis  of,  105 

Table  of,  107 

Unsaturated,  167 
Ethine,  160,  161 

series,  159 
Ethyl,  17 

acetate,  140 

aceto  acetate,  254 

acid  sulphate,  104 

alcohol,  84,  95 

specific  gravity  table,  101 


940 


INDEX 


Ethyl,  amine,  55 

benzene,  481 

bromide,  51 

carbamate,  431 

chlor  carbonate,  524 

chlor  formate,  427 

chloride,  51 

cyanurate,  418 

ether,  107,  108,  159 
Manufacture  of,  108 
Properties  of,  no 

iodide,  51 

iso-cyanurate,  418 

magnesium  iodide,  77 

malonic  acid,  278 

mercaptan,  197 

nitrate,  104 

nitrite,  104,  587 

oxalic  acid,  271 

radical,  17 

sulphate,  104 

sulphonic  acid,  515 

sulphuric  acid,  515 
Ethylene,  151,  154,  157,  158,  463 

bromide,  154 

chloride,  189 

compounds,  189 

Constitution  of,  152 

glycol,  195 

halides,  190 

Preparation  of,  159 

series,  157 

Ethylidene  chloride,  189 
Ethylidene  compounds,  189 
Ethylidene  halides,  189 
Ethylidene  mercaptan,  197 
Eucaine,  896 
Eucalyptol,  828 
Eugenole,  623,  663,  841,  842 
Euler,  846 
Explosives,  Force  of,  379 


Fahlberg,  714 
Fast  red  B,  789 


Fats,  144 

and  oils,  203 

Acids  of,  Table,  204 
Analytical  methods  for,  207 
Bromine  absorption  of,  213 
Chemical  constants  of,  212 
Constants  of,  Table,  216 
Constitution  of,  204 
Hydrolysis  of,  205 
Insoluble  acids  of,  215 
Iodine  value  of,  213 
Koettstorfer  value  for,  2 1 2 
Melting  points  of,  Table,  211 
Physical  constants  of,  210 
Properties  of,  207 
Reactions  of,  205 
Refractive  index  of,  211 
Saponification  number  of,  212 
Saponification  of,  205 
Specific  gravity  of,  Table,  210 
Table  of,  208 
Volatile  acids  of,  215 

Fatty  acids,  Table  of,  209 

Faversham  powder,  534 

Fehling's  solution,  311,  332 

Fenchene,  824 

Fenchone,  825,  835,  841 

Fermentation,  95 
acetic,  135 
alcoholic,  95,  360 
of  carbohydrates,  331 
Theories  of,  96 

Fire  damp,  4 

Fischer,  332,  346,  386,  393,  400,  4 
448,  724,  746,  762 

Fischer  and  Tafel,  340 

Fittig  reaction,  479,  506,  730 

Flax,  370 

Fluorene,  734 

Fluorescein,  618,  759,  760 

Fluoroform,  187 

Formaldehyde,  119 

Formamino  phenol,  633 

Formanilide,  557 

Formic  acid,  131,  134 

Formic  nitrile,  410 


INDEX 


941 


Formose,  340 

Formyl  acetic  acid,  253 

Frankland  reaction,  16,  24,  50,  77,  730 

Freezing-point  constants,  925 

Freezing-point  lowering,  Determination 

of,  925 
Friedel-Craft   reaction,    479,    649,    674, 

679»  730,  735>  702 
Friedlander,  762 
Fritzsche,  539 
Fructosazone,  327 
Fructose,  260,  324,  340,  352,  363 

Inactive,  341 
Fructose ne,  328 
Fruit  flavors,  144 
Fruit  sugar,  352 
Fuchsin,  746 
Fulminic  acid,  419 
Fumaric  acid,  176,  290,  293,  592 

isofnerism  with  maleic  acid,  291 

Synthesis  of,  290 
Furfural,  338,  620,  850 

from  pentosans,  851 
Furfuran,  850 
Furfuryl  alcohol,  852 
Fusel  oil,  101 


Galactans,  366,  380 

Galactose,  351 

Gallic  acid,  619,  722 

Gallo-tannic  acid,  723 

Gas  liquor  salt,  496 

Gasoline,  40,  42 

Gattermann,  599 

reaction,  599,  677 
-Koch  reaction,  649,  660 

Gay  Lussac,  66 

Gelatin  powder,  203,  378 

Geometric  isomerism,  176,  292,  592 

Geranial,  170 

Geraniol,  167,  170,  816,  827,  842,  843 

Geraniyl  acetate,  842 

Globulins,  398 


Glucose,  95,  324,  333,  340,  344,  347, 
35i,  352,  353,  354,  359,  360, 
362,  380,  381 

Alpha  and  beta,  346,  348,  350 

from  formaldehyde,  340 

from  glycerol,  340 

Lactone  constitution  of,  345,  347 

Muta-rotation  of,  345 

phenyl  hydrazone,  581 

Stereo-isomers  of,  Table,  344 
Glucosides,  Alpha  and  beta,  346 
Glucosone,  328,  582 
Glucuronic  acid,  253,  325 
Glutamine,  391 
Glutaminic' acid,  288,  391 
Glutaric  acid,  285 

by  aceto  acetic  ester  synthesis, 

286 

by  malonic  ester  synthesis,  287 
from  propane,  286 
Synthesis  of,  286 
Glutaric  anhydride,  287 
Glutelins,  398 
Gluten,  393 
Glyceric  acid,  201 
Glyceric  aldehyde,  229,  320,  337 
Glycerin,  198 
Glycerol,  198 

chlor  hydrines,  224 

Derivatives  of,  200 

esters,  207 
Table,  208 

Ethers  of,  200 

Inorganic  acid  esters  of,  201 

Organic  acid  esters  of,  203 

Oxidation  products  of,  200 

Properties  of,  199 

Salts  of,  200 

Synthesis  of,  198 
Glycerose,  201,  320,  337,  341,  363 
Glyceryl  acetates,  203 
Glyceryl  mono-chloride,  201 
Glyceryl  mono-nitrate,  202 
Glyceryl  tri-nitrate,  202 
Glyceryl  tri-palmitate,  204,  206 
Glycine,  388,  686 


942 


INDEX 


Glyco-leucine,  390 

-proteins,  398 
Glycogen,  361,  379 
Glycogenase,  362 
Glycol,  195 

chlor  hydrine,  224 
Glycolic  acid,  244 
Glycolic  aldehyde,  229 
Glycolide,  245 
Glycols,  195 

Aromatic,  645 
Glycolyl  urea,  438 
Glycuronic  acid,  253 
Glycyl  alanine,  401 
Glycyl  glycine,  387 
Glyoxal,  261 
Glyoxylic  acid,  252,  297 

reaction,  406 
Glyoxylyl  urea,  439 
Goats'  milk  fat,  208 
Goessmann,  181 
Goldschmidt  Process,  269 
Gomberg,  762 
Graebe,  769 

and  Liebermann,  80 1 
Grape  sugar,  351 
Green,  762 
Griess,  486,  569,  573,  586 

reaction,  569 
Grignard  reaction,  77,  174,  642,  677, 

680,  828 

Grignard  reagent,  77 
Guaiacol,  617,  621,  662 

carbonate,  622 
Guanidids,  441 
Guanidine,  439 
Guanine,  439,  448,  901,  903 
Guano,  439 
Gum  catechin,  722 
Gun-cotton,  375,  379 
Gutta-percha,  843 

H 

Hall,  43 

Halogen  acids,  230,  703 
Aromatic,  704 


Halogen  acids,  Properties  of,  232 

Reactions  of,  233 
Halogen  alcohols,  22 
Halogen  aldehydes,  226 
Halogen  alkanes,  45 
Halogen  anilines,  557 
Halogen  benzenes,  503,  507 

Reactions  of,  505 
Halogen  carriers,  504 
Halogen  hydrines,  223 
Halogen  ketones,  228 
Halogen  phenols,  625 
Halogenation  of  acids,  230 
Halogens  by  Carius  method,  921 
Hantzsch,  591,  746 
Heavy  oil,  497 
Hehner  value,  215 
Helianthine,  574 
Heliotropin,  624,  662,  664,  665 
Heller's  ring,  test,  407 
Hemelithene  486,  491 
Hemi-cellulose,  366 

-terpenes,  815 
Hemo-globins,  396,  399 
Hemp,  370 

oil,  208,  210,  211,  215,  216 
Heptoses,  317 
Heptyl  benzene,  476 
Heroine,  892 
Herzig,  762 
Herschel,  306 
Hesperidene,  819 
Hess,  369 

Hetero-cyclic  compounds,  194,  458,  849 
Hexa-carboxy  benzene,  695 

-chlor  benzene,  505 

-chlor  ethane,  192,  265 

-decyl  benzene,  477 

-di-ine,  163,  167,  467 

-ethyl  benzene,  477 

-hydro  benzene,  468,  504,  811,  812 

-hydro  cymene,  817 

-hydro  terre  phthalic  acid,  694 

-methyl  benzene,  476 

-methylene,  461,  464,  468,  504,  694 
Hexagon  formula,  469,  471 


INDEX 


943 


Hexanes,  18,  25,  29 
Hexosans,  380 
Hexoses,  317,  334,  339 

Synthesis  of,  339 
Hippuric  acid,  388,  681,  684,  686 
Histidine,  390 
Histones,  398 
Hofmann,  54,  71,  539,  555,  746 

iso-nitrile  reaction,  185 

reaction,  71,  148,  685,  709,  88 1 
Holde,  43 
Holland,  217 
Homologous  series,  21 
Hopkins-Cole  reaction,  406 
Horbaczewski,  442,  445 
Hordenine,  906 
Hiibl  solution,  214 
Hiibl-Wijs,  213 
Human  fat,  208,  215,  216 
Hydantoin,  438,  457 
Hydracrylic  acid,  172,  242,  245,  697 

Synthesis  of,  246 
Hydrazides,  584 
Hydrazines,  63,  64,  579 
Hydrazo  benzene,  537,  563,  577 

Rearrangement  of,  578,  732 
Hydrazo  compounds,  577 
Hydrazoic  acid,  63,  64 
Hydrazones,  124,  581,  651 
Hydrines,  202,  223 
Hydro-aromatic  compounds,  811 

-benzenes,  811 

-naphthylamines,  781 

-phthalic  acids,  693 

-quinolines,  864 
Hydrocarbons,  3,  19,  35,  36,  151,  161 

Benzene  series  of,  466 

from  acids,  133 

Higher,  36 

Isomeric,  23,  36 

Mono-substitution  products  of,  45 

Nomenclature  of,  21,  35 

Oxidation  of,  289,  290,  669 

relation  to  acids,  1 29 

Table  of,  19 

Unsaturated,  151,  161 


Hydrocinnamic  acid,  697 

from  malonic  ester,  697 
Hydrocyanic  acid,  66,  409 
Constitution  of,  411 
Synthesis  of,  412 
Hydroferrocyanic  acid,  414 
Hydrogen,  by  combustion,  918 
Hydrogenated  benzene  compounds,  8u 
Hydrolysis,  141,  205 
Hydroquinol,  618 
Hydroquinone,  618 
Hydroxy  acetic  acid,  244 
Hydroxy  acids,  235,  704 

Alpha,  Anhydrides  of,  241 
Anhydrides  of,  241 
Aromatic,  714 
Beta,  Anhydrides  of,  242 
Esters  of,  240 
Ethers  of,  239 
from  amino  acids,  237 
from  cyan  hydrines,  237 
from  halogen  acids,  236 
from  poly-hydroxy  alcohols,  238 
from  unsubstituted  acids,  238 
Gamma,  Anhydrides  of,  242 
Reactions  of,  239 
Reduction  of,  243 
Synthesis  of,  236 
Hydroxy  aldehydes,  228,  658 
anthraquinone,  797 
azo  benzene,  566 
azo  compounds,  576 
benzaldehyde,  658 
benzene,  613 
benzoic  acid,  714 
butyric  aldehyde,  229 
cinnamic  acid,  726 
compounds,  Mixed,  222 
di-basic  acids,  295 
formic  acid,  244,  428 
ketones,  228 
malonic  acid,  201,  296 
-methyl  benzoic  acid,  701,  714, 

728 

naphthalenes,  782 
phenyl  acetic  acid,  714 


944 


INDEX 


Hydroxy  propionic  acids,  172,  245 

pyridines,  857 

quinolines,  863 

stearic  acids,  179 

succinic  acids,  297 

tri-basic  acids,  312 
Hydroxyl  amine,  63,  125,  319 
Hydroxyl    amines,    Rearrangement    of, 

631 

Hydroxyl  compounds,  78 
Hydroxyl  derivatives,  606 
Hyoscyamine,  892 
Hypobromite  reaction,  435 
Hypogaeic  acid,  180,  204,  209,  216 
Hypogaein,  208 
Hypoxanthine,  450,  900,  903 


Identification  of  organic  compounds,  915 

Illuminating  gas,  494 

Imino  formic  acid  chloride,  660 

Imino  urea,  439 

Imitation  camphor,  823 

Immersion  refractometer,  212 

India  rubber,  814 

Indican,  883 

Indigo,  539,  706,  708,  747,  766,  860,  871, 

878,  882 
Baeyer  and  Drewsen  synthesis  of, 

879 
Baeyer  and  Emmerling  synthesis, 

of,  874 
carmine,  883 
Engler  and  Emmerling  synthesis  of, 

873 

from  benzaldehyde,  879 
from  di-phenyl  di-acetylene,  873 
from  naphthalene,  880 
from  nitro  aceto  phenone,  875 
from  nitro  cinnamic  acid,  876 
from  nitro  phenyl  acetic  acid,  876 
from   nitro   phenyl  propiolic   acid, 

876 
from  phenyl  glycine  carboxylic  acid, 

880 


Indigo,  Heumann's  synthesis  of,  880 
Industrial,  882 
Natural,  883 
Synthetic,  708,  873 

History  of,  882 
white,  883 
Indole,  389,  866,  872 

from  nitro  cinnamic  acid,  874 
Indophenin  reaction,  852 
Indoxyl,  866,  869,  881 
Ink,  725 

Inner  anhydrides,  234 
Inner  salt,  Sulphanilic  acid  as,  560 
Inorganic  compounds,  i 
Inositol,  814 
Inulase,  362 
Inulin,  361,  379 
Inversion,  352 
Invert  sugar,  352 
Invertase,  353 
Iodine  reaction,  362 
Iodine  value,  213 
lodo  benzene,  507 

dichloride,  507 
lodo  benzoic  acid,  701,  705 
lodo  ethane,  51 
lodo  methane,  51 
lodoform,  186 

test  for  alcohol,  186 
lodol,  854 

lodonium  compounds,  508 
lodonium  hydroxide,  509 
lodoso  benzene,  508 
lodoso  benzoic  acid,  705 
lodoxy  benzene,  508 
lodoxy  benzoic  acid,  705 
lonone,  816 
Ipatiew,  846 

Iron  cyanide  compounds,  414 
Isatin,  707,  866,  868,  872 

from  nitro  benzoic  acid,  707 

chloride,  872 
Iso-butane,  28 

-cinnamic  acid,  699 

-compounds,  27 

-crotonic  acid,  174,  177,  292 


INDEX 


945 


Iso-cyanates,  73 

-cyanic  acid,  416 

-cyanides,  69 

-cyclic  compounds,  466 

-dialuric  acid,  438 

-diazo  benzene,  548 

-eugenole,  623,  663,  664 

-leucine,  390 

-linolenic  acid,  204,  209 

-linolenin,  208 

-nitrile  reaction,  71,  186 

-nitriles.  69 

-oleic  acid,  180 

-phthalic  acid,  693 

-propyl  benzene,  491 

-propyl  iodide,  28,  51 

-quinoline,  865,  890 

-safrole,  624,  663,  664 

-succinic  acid,  278 

-thio-cyanates,  73,  421 
Isomerism,  21 

Geometric,  292 

of  acids,  130 

of  anthracene  derivatives,  800 

of  benzene  derivatives,  471 

of  butenes,  157 

of  chlor  toluenes,  512 

of  cinnamic  acids,  698 

of  crotonic  acids,  176 

of  di-chlor  ethanes,  188 

of  diazotates,  591 

of  esters,  142 

of  glucoses  and  glucosides,  348 

of  maleic  and  fumaric  acids,  291 

of  naphthalene  derivatives,  775 

of  unsaturated  phenols,  622 

Position,  473 

Stereo,  88 

Structural,  23 
Isomers,  29 
Isoprene,  162,  815,  845 

Synthesis  of,  846 
Ita-conic  acid,  294,  315 


Jute,  370 

60 


K 

Kairolines,  864 
Kekule,  474,  589,  675 

benzene  formula,  474 

-Hantzsch  diazo  formulas,  592 
Kerosene,  40 
Keto  formula,  256 
Keto-hexose,  340 
Ketone  acids,  251,  253 
Ketone  alcohols,  228 
Ketone  hydrolysis,  258 
Ketones,  120 

Aromatic,  647,  657 

Constitution  of,  122 

from  acids,  133 

Hydroxy,  288 

Names  of,  124 

Substituted,  226 

Table  of,  119 

Ketoximes,  Isomerism  of,  653 
Kiliani,  318 

Kjeldahl  method  for  nitrogen,  919 
Knorr,  formula  for  morphine,  890 
Koettstorfer  value,  212 
Kolbe  synthesis,  716 
Kompa  synthesis,  835 
Konig,  constitution  of  quinine,  888 
Korner's  orientation,  486 
Kossel,  393 
Kutscher,  393 


Lactic  acid,  246 

anhydride,  242,  248 

Dextro,  250 

Inactive,  250 

Levo,  251 

Stereo-isomerism  of,  249 
Lactide,  242,  248 

Lactone  constitution  of  glucose,  345 
Lactones,  243 
Lactophenine,  635 
Lactose,  358,  359 
Ladenburg,  475,  885 

benzene  formula,  475 


946 


INDEX 


Lard,  208,  210,  211,  213,  215,  216 

Laurel  oil,  208,  211,  215,  216 

Laurent,  771 

Laurie  acid,  131,  204,  209,  216,  217 

Laurin,  208 

Lead  glycerate,  200 

LeBel,  89 

Lecithin,  906 

Constitution  of,  907 
Lecitho-proteins,  399 
Leucine,  390 
Leuco  base,  738,  740 
Levulinic  acid,  260 
Levulose,  260,  352 
Lewkowitsch,  210 
Liebermann's  nitroso  reaction,  613 
Liebig,  14,  96,  250,  686 

and  Soubeiran,  184 

and  Wohler,  14,  66,  442,  655,  681 

method  for  sulphur,  921 
Light  oil,  467,  497 

Distillation  of,  498 
Lignins,  367 
Ligno-cellulose,  367 
Ligroine,  40 

Limonene,  832,  841,  842 
Limonenes,  819 
Linalol,  842 
Linalyl  acetate,  842 
Linoleic  acid,  181,  204,  209,  214,  216 
Linolein,  208,  213 

Linolenic  acid,  181,  204,  209,  214,  216 
Linolenin,  208 

Linseed  oil,  208,  210,  211,  213,  215,  216 
Litmus,  618 
Loew,  340 
Loiponic  acid,  887 
Lutidines,  858 
Lysine,  391 

M 

Maclurin,  724 

Madder,  800 

Magenta,  746 

Magnesium  alkyl  halides,  77 

Maize  oil,  208,  215,  216 


Malachite  green,  655,  747 
Maleic  acid,  176,  290,  293,  592 

anhydride,  292 

tsomerism  of,  291 

Synthesis  of,  290 
Malic  acid,  297 

Active,  300 

and  maleic  acid,  298 

Inactive,  300 

Isomerism  of,  299 
Malonamide,  278 
Malonic  acid,  273 

Derivatives  of,  277 

Esters  of,  275 

Homologues  of,  274,  278 

Reactions  of,  274 

syntheses,  274 

synthesis  of  glutaric  acid,  287 
Malonyl  chloride,  278 
Malonyl  urea,  438 
Malt,  360 

Maltase,  96,  360,  363 
Maltose,  360 
Mandellic  acid,  728 
Mannans,  366,  380 
Mannitol,  219,  339 
Mannose,  339,  344 
Maple  sap,  354 
Marsh  gas,  4 
Martius,  576 

yellow,  785 
Mauve,  541,  744 
Medicus,  442 
Melibiose,  361 
Mellitic  acid,  695 

Melting-point,  Determination  of,  915 
Mendelejeff ,  43 
Mentha-di-ene  ke tones,  831 
Mentha-di-enes,  819 
Menthanes,  817,  818 
Menthanol,  825 
Menthanone,  825 
Menthenes,  817,  818 

Derivatives  of,  828 

Isomerism  of,  818 
Menthol,  825,  841,  842 


INDFX 


947 


Menthone,  825,  842 

Mercaptals,  197 

Mercaptans,  197 
Aromatic,  646 
Di-valent,  197 

Mercaptols,  197 

Mercer,  372 

Mercerized  cotton,  368,  372 

Mercuric  cyanide,  66 

Mercuric  fulminate,  419 

Mercuric  thio-cyanate,  420 

Mesa-conic  acid,  293 

Mesitylene,  476,  486,  487,  496,  498 
carboxylic  acid,  687 
from  acetone,  489 
from  allylene,  478,  489 
Oxidation  of,  487 
Synthesis  of,  489 

Mesitylenic  acid,  487,  695 

Meso-tartaric  acid,  305 

Mesoxalic  acid,  252,  296 

Mesoxalyl  urea,  439 

Meta,  472 

-chloral,  227 
-proteins,  399,  406 

Metaldehyde,  117 

Metallic  alkyl  compounds,  76 

Methanal,  119 

Methane,  4 

a  saturated  compound,  n 
a  symmetrical  compound,  n 
Chemical,  properties  of,  5 
di-carboxylic  acid,  273 
from  carbides,  6 
from  sodium  acetate,  7 
Laboratory  preparation  of,  6 
Physical  properties  of,  5 
reaction  with  halogens,  7 
series,  4 
Structure  of,  10 
Synthesis  of,  6 

Methanoic  acid,  131,  134 

Methan-ol,  84,  94 

Methose,  340 

Methyl,  14 

acrylic  acid,  174 


Methjl,  alcohol,  84,  94 

amine,  54 

amine  hydriodide,  56 

amines,  63 

ammonium  iodide,  56,  57 

anilines,  546 

Rearrangement  of,  554 

anthranilate,  710,  842 

benzene,  479 

buta-di-ene,  162,  815 

butan-ol,  88,  90 

bromide,  15 

carbylamine,  71 

chloride,  15,  51 

cro tonic  acids,  178 

cyanide,  68,  411 

di-chlor  benzenes,  513 

ether,  107 

ethyl  ether,  107 

ethyl  ketone,  119 

halides,  15 

iodide,  15,  51 

iso-cyanate,  73 

iso-cyanide,  70,  73,  411 

iso-propyl  benzene,  492 

iso-propyl  ketone,  119 

malonic  acid,  278 

orange,  573 

phenyl  ether,  720 

phenyl  nitrosoamine,  551 

propenoic  acid,  173 

pyridines,  858 

pyrrolidine,  846 

radical,  16 

salicylate,  718,  841,  842 

succinic  acid,  284 

violet,  553 

zinc  iodide,  76 
Methylene  mercaptan,  197 
Methylenitan,  340 
Metol,  633 
Meyer,  657,  762,  852,  921 

and  Jacobson,  293 
Michler's  ketone,  667,  734 
Middle  oil,  497,  765 
Milk  sugar,  358 


948 


INDEX 


Millon's  reaction,  405 

Mitscherlich,  306 

Moissan,  6,  43 

Molecular  weight,  Calculation  of,  926 

Determination  of,  925 
Mono-amino  substitution  products,  5  4 

-brom  methane,  15 

-chlor  acetic  acid,  234 

-chlor  benzene,  505 

-chlor  ethane,  17 

-chlor  hydrine,  202 

-chlor  methane,  8,  13,  15,  52 

-chlor  toluene,  510 

-halogen  ethenes,  164 

-halogen  methanes,  15 

-halogen  substitution  products,  45 

-hydroxy  benzenes,  613 

-hydro xy  cymenes,  615 

-hydroxy  succinic  acid,  297 

-hydroxy  toluenes,  614 

-hydroxyl  compounds,  78 

-iodo  methane,  15 

-methyl  aniline,  550 

-nitro  benzene,  530 

-nitro  phenol,  629 

-saccharoses,  317,  334,  336 
Morphine,  890 
Moth  balls,  765 
Mucic  acid,  344 
Mucin,  396 
Muscarine,  908 
Musk,  Artificial,  535 
Muta-rotation,  345,  349 
Myristic  acid,  131,  204,  209,  216,  217 
Myristin,  208 


X 


Naphthalene,  496,  498,  689,  765 
Anthranilic  acid  from,  708 
Constitution  of,  766,  769 
Derivatives  of,  375 
Formula  for,  770 
from  coal  tar,  765 
from  phenyl  butylene  bromide,  767 
from  phenyl  vinyl  acetic  acid,  768 


Naphthalene,  from  tetra-carboxy  ethane, 
768 

Halogen  derivatives  of,  777 

Isomerism  of  derivatives  of,  775 

Phthalic  acid  from,  766 

Source  of,  765 

sulphonic  acids,  782 

Synthesis  of,  767 

tetra-chloride,  777 

Uses  of,  766 
Naphthalic  acids,  791 
Naphthalic  anhydride,  792 
Naphthenes,  38,  811 
Naphthionic  acid,  786,  787 
Naphthoic  acids,  791 
Naphthol,  497,  782 

blue  black,  788 

dyes,  783 

sulphonic  acids,  786 

Synthesis  of,  783 

yellow  S,  785 

Naphthoquinones,  790,  795 
Naphthyl  salicylate,  784 
Naphthylamine,  779 

sulphonic  acids,  786 
Naphthylamines,  779 

Diazotization  of,  780 

from  naphthols,  779 

Hydrated,  781 

reagent  for  nitrites,  780 

relation  to  dyes,  780 

Tetra-hydro,  772 
Narcotine,  890 
Natural  gas,  4 
Nef,  350 

Neurine,  906,  908 
New  orthoform,  898 
New-mown  hay,  727 
Nichols  medal,  762 
Nicotine,  858,  886 
Nicotinic  acid,  858,  886 
Nietski,  746 
Nitraniline,  562 
Nitric  acid,  Reduction  of,  536 
Nitro,  529 

aceto  phenone,  875 


INDEX 


949 


Nitro,  acids,  703 

alkyl  benzenes,  535 
anilines,  559 
aromatic  acids,  705 
benzaldehyde,  879 
benzene,  529,  530 

Reduction  products  of,  535,  537 
Benzoic  acids,  705 
cellulose,  368,  375 
cinnamic  acid,  701,  710,  874,  876 
compounds,  528 
Alkyl,  74 
Reduction  of,  529 
glycerin,  202,  376 
glycerol,  202,  376,  379 
methane,  75 
naphthalenes,  770,  778 
naphthols,  785 
phenols,  629 
phenyl  acetic  acid,  876 
phenyl  propiolic  acid,  876 
toluenes,  531 
xylenes,  534 
Nitrogen,  55 

by  Dumas  method,  919 
by  Kjeldahl  method,  919 
compounds,  Intermediate,  563 
derivatives,  Resume  of,  604 
Fixation  of,  422 
Pentavalent,  55 
Trivalent,  55 
Nitrosamine,  551 
Nitroso  amines,  61,  76 
anilines,  558 
benzene,  536,  538,  563 
compounds,  74,  538 
di-methyl  aniline,  548,  552 
methyl  aniline,  551,  559 
naphthol,  791 

phenol,  Constitution  of,  628 
phenols,  553,  627,  640 
Nitrous  acid,  .Reaction  with  amines,  546 
Nobel,  203,  378 
Nolting,  486 
Nomenclature,  29,  31 

of  substituted  acids,  231 


Nomenclature,  Systematic,  29 
Nonoses,  317 
Nonylenic  acid,  172 
Normal  butane,  28 
Normal  compounds,  27 
Novocaine,  898,  899 
Nucleic  acids,  904 
Nucleo-proteins,  398 
Nutmeg  oil,  208 
Nux  vomica,  890 


0 


Octa-deca-peptide,  402 
Octa-decyl  benzene,  477 
Octa-tri-ene,  Di-methyl,  163 
Octoses,  317 
Octyl  benzene,  476 
Oenanthylic  acid,  131 

Oil,  37 

of  anise,  842 
bergamot,  820 
bitter  almonds,  655,  843 
cajeput,  828 
camphor,  842 
caraway,  820 
cardamon,  820,  828 
cassia,  842 
cinnamon,  699,  842 
citronella,  819 
clove,  842 
cumin,  820 
dill,  820,  831 
eucalyptus,  820,  827 
fennel,  820 
garlic,  168,  420 
geranium,  816,  842 
ginger,  825 
kummel,  831 
lemon,  819,  842 
lemon  grass,  842 
marjoram,  828 
mustard,  165,  421 
neroli,  819,  842 

olive,  208,  210,  211,  213,  215,  216 
orange,  842 


950 


INDEX 


Oil  of  orange  blossoms,  819,  842 
orange  peel,  819 
peppermint,  820,  825,  842 
pine  needles,  820,  842 
rose,  842 
rosemary,  842 
spearmint,  820,  842 
spike,  825 
tansy,  842 
thuja,  835 
turpentine,   814,   820,   823,   825, 

827,  842 
valerian,  825 
wintergreen,  93,  718,  842 
Ylang-Ylang,  842 
Oils,  Petroleum,  37 
Essential,  66 1,  840 

Table  of,  842 
Illuminating,  40 
Light,  40,  497 
Lubricating,  40 

Oleic  acid,  178,  204,  209,  214,  216,  217 
Constitution  of,  1 79 
Elaidic  acid  from,  179 
Olein,  207,  208,  213 
Oleo-ref ractometer,  2 1 2 
Open  chain  compounds,  20 
Opium,  890,  891 

Alkaloids  of,  891,  892 
Orange  II,  783 
Orcein,  618 
Orcinol,  618 

Organic  chemistry,  Definition  of,  2 
Organic  compounds,  i 
Analysis  of,  917 
Identification  of,  915 
Purification  of,  913 
Separation  of,  913 
Organo  metallic  compounds,  76 
Orientation,  482 
Ornithuric  acid,  687 
Ortho,  472 
Orthoform,  898 
Ortho-formic  acid,  185 
Orthoquinone,  639 
Osazones,  327,  582 


Osborne,  393 
Oscillation  theory,  474 
Osones,  328,  582 
Ostwald,  756,  762 
Oxalic  acid,  264,  408 

Amides  of,  271 

Chlorides  of,  271 

Commercial  preparation  of,  269 

Esters  of,  271 

from  cyanogen,  264 

from  glycol,  265 

from  hexa-chlor  ethane,  265 

Properties  of,  270 

relation  to  formic  acid,  266 

Salts  of,  271 

Synthesis  of,  264 
Oxalyl  chloride,  272 
Oxalyl  urea,  438 
Oxamic  acid,  272 
Oxamide,  272 
Oxanilic  acid,  557 
Oxanilide,  557 
Oxidation    products    of    hydrocarbons, 

scheme,  289 

Oxidation  reactions,  127 
Oximes,  124,  651 

of  quinone,  637 
Oxindole,  708,  866 
Oxonium  compound,  349 
Oxy-hemoglobin,  394 

-proline,  392 

-purine,  900 


Palm  oil,  208,  210,  211,  213,  215,  216 
Palmitic  acid,  131,  137,  204,  209,  216, 

217 

Palmitin,  207,  208,  213 
Papaverine,  890 
Paper,  370 

Parchment,  372 

Production  of,  372 
Para,  473 
Para  rubber,  843 
Parabanic  acid,  438,  443 


INDEX 


951 


Paraffin,  4,  38,  43 

series,  4 
Paraffins,  3,  5,  u 

Table  of,  19 
Paraldehyde,  117 
Pararosaniline,  738 

chloride,  739 

leuco  base,  738 

Preparation  of,  742 
Pararosolic  acid,  748 
Pasteur,  89,  91,  96,  306 
Peanut  oil,  208,  210,  211,  215,  216 
Pectins,  338,  367 
Pecto-cellulose,  367 
Penta-chlor  benzene,  505 

-chlor  toluene,  510 

-ethyl  benzene,  476 

-hydro xy  pentane,  218 

-methyl  benzene,  476 

-methylene,  461,  464 

di-amine,  194,  856,  905 
Pentan-di-oic  acid,  285 
Pentane,  18,  25 

Methyl,  33 

Normal,  29 
Pentanols,  85,  101 
Pentosan  reagent,  620 
Pentosans,  338,  366,  380 
Pentoses,  317,  334,  33$ 
Pentyl  iodide,  Normal  29 
Pepper,  665,  858,  886 
Pepsin,  96,  404 
Peptones,  399 
Per-chlor  ethane,  192 
Perfumes,  840 
Perkin,  744,  762 

-Fitting  synthesis,  171,  172 

medal,  745 

reaction,  Cinnamic  acid  by,  698 

synthesis,  828 

of  coumarin,  727 
Petroleum,  4,  37 

and  its  products,  39 

Chemical  character  of,  37 

Distillation  products  of,  38,  41 

Heat  of  combustion  of,  39 


Petroleum,  Occurrence  of,  37 

Origin  of,  43 

Physical  properties  of,  37 

Yield  of  products  from,  42 
Phellandrene,  820,  842 
Phenacetine,  634 
Phenanthraquinone,  809 
Phenanthrene,  496,  499,  765,  792,  806, 
807 

and  derivatives,  806 

from  amino  phenyl  cinnamic  acid, 
807 

from  brom  benzyl  bromide,  809 

from  di-tolyl,  806 

from  stilbene,  806 

Synthesis  of,  806 
Phenetidine,  634 
Phenetole,  612,  621 
Phenocoll,  635 
Phenol,  496,  613 

acids,  714,  726 

aldehydes,  658 

as  antiseptic,  614 

Commercial  preparation  of,  614 

ethers,  621,  66 1 

sulphonic  acids,  626 
Phenolates,  611 
Phenolphthalein,  691,  750 

a    tri-phenyl    methane    derivative, 

750 

Color  of,  753,  756 
Constitution  of,  753 
Preparation  of,  750 
Pyronine  constitution  of,  756 
•     Quinoid  constitution  of,  754 
Phenols,  498,  606,  613 

Color  reactions  of,  613 

Derivatives  of,  621 

Esters  of,  611 

Ethers  of,  612 

from  aryl  halides,  610 

from  diazo  compounds,  597,  608 

from  hydrocarbons,  609 

from  hydroxy  acids,  609 

from  sulphonic  acids,  520,  522,  608 

Natural  sources  of,  610 


952 


INDEX 


Phenols,  Properties  of,  610 
Reactions  of,  610,  612 
Salts  of,  611 
Substituted,  624 
Synthesis  of,  608 
Unsaturated,  622 
Phenyl,  493 

acetate,  611 

acetic  acid,  672,  673,  679,  696 

acetylene,  494 

acrylic  acid,  656,  697,  699 

acrylic  aldehyde,  656 

alanine,  389,  701,  711 

butylene  bromide,  767 

crotonic  acid,  700 

cyanide,  521,  599,  652 

ethyl  sulphide,  524 

ethyl  sulphone,  524 

ethyl  thio-ether,  524 

ethylehe,  493 

glycine,  561 

glycine  ortho-carboxylic  acid,  710, 

869,  880 

glycolic  acid,  728 
hydrazine,  64,  125,  319,  563,  580 

as  carbohydrate  reagent,  581 

Derivatives  of,  583 

Reactions  of,  326,  581 
hydrazones,  326,  581 
hydroxy  acetic  acid,  714 
hydroxyl  amine,  536,  563 

Rearrangement  of,  564 
iodonium  hydroxide,  508 
iodoso  chloride,  507 
iso-cyanate,  685 
iso-succinic  acid,  680 
maleic  acid,  673 
malonic  acid,  679 
methyl  ketone,  657 
methyl  ketoxime,  654,  657 
methyl  nitrosamine,  559 
nitroso  amine,  547,  592 

Rearrangement  of,  587 
ortho-tolyl  ketone,  794 
propene,  493 
propine,  494 


Phenyl;  propiolic  acid,  696,  700 

propionic  acid,  679,  697 

salicylate,  719 

sodium  carbonate,  717 

succinic  acid,  673,  679 

sulphuric  acid,  626 
-  tolyl  ketone,  794 

tolyl  ketoxime,  654 

tolyl  sulphone,  526 

vinyl  acetic  acid,  700,  768 
Phenylene  di-amines,  561,  574 
Phloroglucid,  338,  620 
Phloroglucinol,  338,  620,  812 

Tautomerism  of,  620,  813 
Phosgene,  184,  187,  429 
Phosphines,  64 
Phosphonium  hydroxide,  65 
Phosphonium  iodide,  64 
Phosphonium  salts,  64 
Phospho-proteins,  398 
Phosphorus  compounds,  64 
Photographic  developers,  633 
Photo-synthesis,  363 
Phthalamide,  691 
Phthalamidic  acid,  709 
Phthalein  dyes,  691,  750 
Phthalic  acid,  673,  687 

anhydride,  690,  707 

from  naphthalene,  689,  766,  777 

Hydro,  693 

Meta,  693 

Para,  693 

relation  to  indigo,  880 

relation  to  xylene,  687 

Synthesis  of,  688,  689 
Phthalide,  728,  751 
Phthalimide,  691,  707,  709 

Ethyl,  691 

Ethylene,  692 

Potassium,  691 
Phthalophenone,  751 
Phthalyl  chloride,  692,  728,  751 
Phytin,  814 
Picolines,  858  ' 
Picrate  explosives,  631 
Picric  acid,  630 


INDEX 


953 


Pictet,  886 

Pinane,  823 

Pinene,  823,  838,  841,  842 

hydrochloride,  823,  838 
Pinner,  886 

Piperic  acid,  665,  858,  886 
Piperidine,  194,  856,  858,  886,  905 
Piperidon,  456,  849 
Piperine,  665,  858,  886 
Piperonal,  624,  662,  665 
Pitch,  497 
Polariscope,  358 
Poly-alcohols,  195 

-amines,  193 

-amino  benzenes,  561 

-carboxy  acids,  264 

-cyanides,  192 

-halides,  182 

-halogen  compounds,  51 
ethanes,  53,  188 
methanes,  52,  182 

-hydroxy  alcohols,  195.  198,  217 
benzenes,  616,  645 
compounds,  195,  198,  616, 

645 

-methylene  compounds,  193,  462 
-peptides,  386,  399 
Synthetic,  402 
Tautomerism  of,  403 
-phenols,  616 
-saccharoses,  334,  361 
-substitution  products,  182,  220 
Poppy  oil,  208,  210,  211,  215,  216 
Potassium  antimonyl  tartrate.  311 
cyanate,  67,  417 
cyanide,  66 
ferri-cyanide,  66,  415 
ferro-cyanide,  66,  415 
indoxyl  sulphate,  871 
picrate,  379 
pyrrole,  856 
tetroxalate,  271 
Primary  compounds,  47 
Prolamins,  398 
Proline,  392,  855 
Proof  spirit,  99 


Propanal,  119 
Propan-di-oic  acid,  273 
Propane,  18 

Di-methyl,  33 

lodo,  51 

Methyl,  32 

Synthesis  of,  20 
Propanoic  acid,  131 
Propanone,  124 
Propan-tri-ol,  198 
Propargyl,  163 

alcohol,  167 
Propenal,  168 
Propene,  157 
Propenoic  acid,  172,  245 
Propenol,  166 
Propine,  161 
Propinoic  acid,  181 
Propiolic  acid,  181 
Propionic  acid,  131 
Propyl,  20 

amine,  55 

benzene,  491 

ether,  107 

iodide,  22,  28,  51 

piperidine,  858,  885 

propane,  30 

pyridine,  858 
Propylene,  157 

glycol,  196 
Protamines,  398 
Proteans,  399 
Proteases,  404 
Protein  salts,  407 
Proteins,  382,  392 

Chemical  properties  of,  395 

Classification  of,  398 

Color  reactions  of,  405 

Composition  of,  394 

Conjugated,  396 

Constitution  of,  399 

iVrivrd,  307 

Hydrolvsis  of,  300,  404 

Hydrolytic  products  of,  3,ss 

Molecular  weight  of,  394 

Physical  properties  of,  395 


954 


INDEX 


Proteins,  Precipitation  tests  for,  406 

Qualitative  tests  for,  405 

Simple,  396 

Tautomerism  of,  403 
Proteolytic  enzymes,  404 
Proteoses,  399 
Protocatechuic  acid,  720 

Constitution  of,  721 

Synthesis  of,  721 
Protocatechuic  aldehyde,  66 1 

Methyl  ether  of,  66 1 
Pseudo-compounds,  628 

-cumene,  486,  490 

-cumidine,  545 

-ionone,  816 

-tannin,  724 
Ptomaines,  904 
Ptyalin,  96 
Pulegone,  831 

Purification  of  organic  compounds,  913 
Purine,  448,  900 

alkaloids,  900 

bases,  425,  448 

Di-hydroxy,  448 

Di-methyl  di-hydroxy,  449 

Tri-hydroxy,  449 

Tri-methyl  di-hydroxy,  449 
Purpurin,  806 

Putrescine,  193,  194,  854,  905 
Pyrene,  810 
Pyridine,  497,  856,  860 

Carboxylic  acids  of,  857 

Derivatives  of,  857 

Homologues  of,  858 

tri-carboxylic  acid,  858 
Pyridyl  methyl  pyrrolidine,  886 
Pyrocatechinol,  617 
Pyro-collodion,  375 

-ligneous  acid,  94 

-mucic  acid,  851 

-racemic  acid,  248,  253 

-tartaric  acid,  284 
Pyrogallic  acid,  619 
Pyrogallol,  619 

in  gas  analysis,  619 

in  photography,  620 


Pyronine  ring,  756 
Pyroxylin,  375 
Pyrrazole,  855 
Pyrrazoline,  855 
Pyrrazolone,  855 
Pyrrole,  850,  853 

Tetra-iodo,  854 
Pyrrolidine,  194,  392,  854,  905 

carboxylic  acid,  855 
Pyrrolidon,  456,  849 
Pyruvic  acid,  253 


Querci-tannic  acid,  724 
Quercitol,  814 
Quina,  888 
Quinic  acid,  638 
Quinidine,  888 
Quinine,  638,  887 

Constitution  of,  888 
Quininic  acid,  887 
Quinoid  structure  of  dyes,  740 
Quinoline,  497,  86 1 

Baeyer  and  Drewsen  synthesis  of, 
861 

carboxylic  acids,  864 

Derivatives  of,  863 

Skraup's  synthesis  of,  862 
Quinolinic  acid,  858,  864 
Quinone,  636,  790,  812 

Constitution  of,  636 

Oximes,  628,  637,  640 

Tautomerism  of,  636 
Quinones,  635 

Derivatives  of,  639 


Racemic  acid,  305,  311 

Racemic  compounds,  Splitting  of,  308 

Radical,  13 

of  benzoic  acid,  655,  681 
Rafftnose,  361 
Reducin,  633 
Redwood,  Boverton,  39 


INDFX 


955 


Refractometers,  211 
Reichert-Meissl  value,  215 
Reimer-Tiemann  reaction,  659,  660,  717 
Remsen,  714 
Resorcinol,  618 

phthalein,  759 
Retene,  810 
Rhamnitol,  218 
Rhamnose,  219,  339 
Rhodamines,  756 
Rhodinal,  633 
Richter,  31,  36 
Ricinoleic  acid,  216 
Ring  carboxy  acids,  680 
Rittman,  43 
Rochelle  salt,  310  • 
Rosaniline,  743 
Rosenstiehl,  746 
Rosin,  840 
Rosolic  acid,  748 
Rubber,  260,  811,  843 

Coagulation  of  the  latex,  843 

Manufacture  of,  844 

Vulcanization  of,  844 
Ruberythric  acid,  800 
Runge,  539,  614 


Sabatier  and  Senderens  reaction,  811 
Saccharic  acid,  325,  344 
Saccharin,  517,  712 

Synthesis  of,  713 
Saccharometer,  358 
Safrole,  623,  663 
Salicin,  646,  718 
Salicylic  acid,  646,  714 

from  amino  benzoic  acid,  715 

from  phenol,  716 

from  sulpho  benzoic  acid,  715 

Kolbe  synthesis  of,  716 

Medicinal  properties  of,  719 

Synthesis  of,  715 
Salicylic  alcohol,  646 
Salicylic  aldehyde,  659,  727 
Salol,  719,  784 


Salts,  137 

Sandmeyer  reaction,  598,  704,  808 

Saponification,  141,  205 

Sarco-lactic  acid,  250 

Sarcosine,  388 

Saturated  compound,  n 

Saturated  hydrocarbons,  n 

Table  of,  19 
Scheele,  250 
Schorlemmer,  746,  806 
Schotten-Baumann  reaction,  684,  686 
Schweitzer's  reagent,  367 
Secondary  compounds,  47 
Seidlitz  powders,  311 
Semi-carbazid,  441 

Separation  of  organic  compounds,  913 
Serine,  389 
Serum  albumin,  394 
Side-chain  carboxy  acids,  Synthesis  of, 

678 

Silk,  Artificial,  373 
Silver  cyanide,  66 
Simpson,  184 
Sisal,  370 
Skatole,  870 
Skraup's  synthesis,  862 
Smokeless  powder,  378 
Soap,  204,  206 
Socrates,  885 
Sodium  acetamide,  684 

alcoholate,  79 

benzamide,  684 

ethylate,  255 

palmitate,  204 

phenolate,  717 

potassium  tartrate,  310 
Sorbitol,  219,  339 
Sorghum,  354 

Specific  gravity,  Determination  of,  916 
Sperm  oil,  216 
Spermaceti,  93,  216 
Standard  Oil  Co.,  43 
Starch,  361,  363 

Hydrolytic  products  of,  364 
Industrial  uses  of,  364 
Iodine  reaction  of,  362 


956 


INDEX 


Starch,  Isolation  of,  365 
Stearic  acid,  131,  137,  204,  209,  216,  217 
Stearin,  207,  208,  213 
Stereo-isomerism,  88 

of  benzaldoxime,  652 

of  diazotates,  591 

of  glucose,  Table,  344 

of  hexa-hydro  terre-phthalic  acid, 

695 

of  maleic  and  fumaric  acids,  291 

of  malic  acid,  299 

of  mono-saccharoses,  342 

of  tartaric  acid,  304 
Stilbene,  762 
Stovaine,  897 
Strain  theory,  462 
Structural  formula,  12 
Strychnine,  889 
Styrene,  493,  699 
Styrin,  699 
Suberic  acid,  289 
Substantive  dyes,  788 
Substituted  acids,  229 
Substituted  ammonias,  539 
Substituted  phenols,  624 
Substitution,  9,  153 
Succinamic  acid,  282 
Succinamide,  282 
Succinic  acid,  278 

Derivatives  of,  280 

from  brom  acetic  acid,  279 

from  ethylene,  278 

from  malonic  ester,  279 

Homologues  of,  284 

Synthesis  of,  278 

Succinic  anhydride,  280,  457,  690,  849 
Succinimide,  283,  457,  691,  707,  849 
Succinyl  chlorides,  282 
Sucrase,  353,  361 
Sucrose,  3,53 
Sugar  beet,  354 
Sugar  cane,  354 
Sugar,  in  urine,  447 
Sugars,  316,  351,  353 
Sulphamine  benzoic  acid,  712 
Sulphanilic  acid,  560,  574,  780 


Sulphinic  acids,  523 

Constitution  of,  524 

Esters  of,  525 
Sulphite  process,  371 
Sulpho  acids,  704 
Sulpho  aromatic  acids,  712 
Sulpho  benzoic  acid,  712 
Sulphon  amides,  519 
Sulphon  chlorides,  519 
Sulphonal,  198 
Sulphones,  524,  526 
Sulphonic  acids,  514 

Character  of,  518 

Esters  of,  520 

Hydrolysis  of,  521 

Reactions  of,  519,  523 

Salts  of,  518 

Sulphur  by  Carius  method,  921 
by  Liebig's  method,  921 
Sulphuric  acid  derivatives,  514 
Sulphuric  acid  esters,  514 
Sun  flower  oil,  210,  211,  215 
Sylvestrene,  820,  841 
Symmetrical  compounds,  n,  189,  473 
Symmetry  of  benzene,  471 
Syn  form,  592 
Synthetic  anesthetics,  895 
Synthetic  dyes,  746 


Tallow,  208,  210,  211,  213,  215,  216 

Tannic  acids,  723 

Tannins,  724 

Tar,  43 

Tartar  emetic,  311 

Tartaric  acid,  301,  338 

Dextro,  304,  309 

from  glyoxal,  302 

from  maleic  acid,  303 

from  succinic  acid,  302 

Isomerism  of,  304 

Levo,  305,  311 

Meso,  305,  312 

Reduction  of,  303 
Tartronic  acid,  296 


INDEX 


957 


Tartronyl  urea,  438 
Tautomerism,  256,  591 

of  aceto  acetic  acid,  256 

of  cyanogen  compounds,  413 

of  diazotates,  591 

of  phloroglucinol,  620 
Terpa-di-ene,  817 
Terpan-di-ol,  827 
Terpane,  817 
Terpanol,  825 
Terpanone,  825 
Terpene,  817 
Terpenes,  616,  814 

Cyclic,  815,  816,  831 

Di-cyclic,  821 

Di-cyclic  derivatives  of,  835 

Olefine,  815 

Oxidation  products  of,  825 

Scheme  of  relationships  of,  832 
Terpin,  827,  829 

hydrate,  827 
Terpinenes,  819,  820 
Terpineol,  828,  829,  841,  842 
Terre-phthalic  acid,  693,  694 
Tertiary  compounds,  47 
Tetra-brom  ethane,  793 

-carboxy  ethane,  276,  768 

-chlor  benzene,  505 

-chlor  methane,  8,  52,  187 

-chlor  toluene,  510 

-hydro  benzene,  812 

-hydro  cymene,  817 

-hydro  naphthylamines,  772 

-hydro  terre-phthalic  acid,  694 

-hydro  toluic  acid,  828 

-hydroxy  butane,  218 

-iodo  pyrrole,  854 

-methyl  ammonium  iodide,  58 

-methyl  ammonium  salts,  58 

-methyl  arsonium  hydroxide,  66 

-methylene,  461,  464 

-methylene   di-amine,     194,    854, 

905 

-peptide,  402 
Tetravalent  carbon,  91 
Tetrazo  compounds,  575,  732,  787 


Tetroses,  317,  334,  337 
Theine,  448,  903 
Theobromine,  448,  901,  903 
Theophylline,  450,  901,  903 
Thio-compounds,  73 

-cyanates,  73 

-cyanic  acid,  416,  420 

-ethers,  Unsaturated,  167 

-phenols,  646 

-sulphonic  acids,  525 

-ureas,  437 
Thiophen,  850,  852 
Thomson  displacement  process,  377 
Thujene,  822 
Thujone,  835,  842 
Thymol,  615,  826 
Tiglic  acid,  178 
Tilden,  846 
Titer,  210 
T.  N.  T.,  378,  532 

Preparation  of,  533 
Tolane,  762 
Tollens,  346,  479 
Toluene,  476,  479,  496,  498 

Chlorine  substitution  products  of, 

5°9 

Oxidation  of,  480* 

sulphon  amide,  713 

sulphon  chloride,  713 

sulphonic  acids,  517,  713 
Toluic  acid,  Alpha,  696 
Toluic  acids,  673,  687 
Toluidines,  544 

Dyes  from,  544 
Tolyl  phenyl  sulphone,  526 
Tri-acetone  amine,  896 

-amino  azo  benzene,  574 

-amino  tri-phenyl  carbinol,  738 

-amino  tri-phenyl  methane,  738 

-azo  compounds,  583 

-azoic  acid,  64 

-basic  acids,  312 

-brom  methane,  186 

-brom  phenol,  625 

-carballylic  acid,  312 

-chlor  acetic  acid,  235 


958 


INDEX 


T  r  i  -chlor  aldehyde,  226 

-chlor  benzene,  504,  505 

-chlor  hydrine,  202 

-chlor  methane,  8,  52,  183 

-chlor  toluenes,  510 

-cresol,  615 

-fluor  methane,  187 

-hydroxy  alcohols,  198 

-hydroxy  benzenes,  619,  813 

-hydroxy  glutaric  acid,  339 

-hydroxy  methane,  185 

-hydroxy  propane,  198 

-hydroxy  purine,  900 

-iodo  methane,  186 

-mesitic  acid,  488,  673,  695 

-methyl  ammonium  iodide,  57 

-methyl  arsine,  66 

-methyl  benzene,  486 

-methyl  hexa-decyl  benzene,  477 

-methyl  pyridines,  858 

-methyl  xanthine,  901 

-methylene,  173,  460,  462,  464 

-methylene  carboxylic  acid,  173 

-methylene  glycol,  196 

-nitro  benzenes,  531 

-nitro  phenol,  629,  630 

-nitro  toluene,  378,  532 

-nitro  tri-phenyl  methane,  738 

-oses,  317,  334,  336 

-oxy  hexa-hydrobenzene,  813 

-oxy  methylene,  340 

-palmitin,  207 

-phenyl  amine,  546,  555 

-phenyl  methane,  735 
Constitution  of,  736 
dyes,  736 
Synthesis  of,  735 

-phenyl  methyl,  762 

-saccharoses,  335,  361 
Triple  bond,  160 
Tris-azo  compounds,  572 
Tropaeolin  D.,  574 
Tropic  acid,  699,  892 
Tropine,  892,  894 
Trypsin,  404 
Tryptophane,  389,  870 


Tunicin,  366 

Turkey  red,  747,  800 

Turpentine,  491,  820,  823,  839,  846 

industry,  839 
Tyrean  purple,  747 
Tyrosine,  389,  701,  726 

U 

Unsaturated  acids,  170 

Di-basic,  289 

Synthesis  of,  170 
Unsaturated  alcohols,  166 
Unsaturated  aldehydes,  168 
Unsaturated  ethers,  167 
Unsaturated  hydrocarbons,  151 
Unsaturated  thio-ethers,  167 
Unsaturation,  151 

Unsymmetrical  benzene  compounds,  473 
Unverdorben,  539 
Uranine,  760 
Urea,  i,  64,  418,  425,  429 

Biological  synthesis  of,  43 1 

Clinical  test  for,  435 

Decomposition  of,  431 

Enzymatic  hydrolysis  of,  434 

Isolation  of,  436 

Occurrence  of,  434 

Physiological  relations  of,  446 

Properties  of,  434 

relation  to  carbonic  acid,  432 

relation  to  formic  acid,  432 

Salts  of,  436 

Synthesis  of,  433 
Ureas,  Alkyl,  436 
Ureids,  437,  43 8 
Uric  acid,  425,  442,  449,  457,  849,  9°° 

Constitution  of,  442 

Enol  formula  for,  449 

Keto  formula  for,  449 

Medicus  formula  for,  443 

Methyl,  444 

Oxidation  products  of,  443 

Properties  of,  446 

Physiological  relations  of,  446 

Syntheses  of,  445 

Tautomerism  of,  449 


INDEX 


959 


Urine,  436,  446 

Albumin  in,  447 

Analysis  of,  447 

Nitrogen  of,  446 

nitrogen,  per  day,  447 

Sugar  in,  447 
Uvitic  acid,  488,  695 

V 

Valeric  acids,  131,  136 
Valero  lactam,  456 
Valine,  390 
Vanilla  extract,  66  1 
Vanillic  acid,  722 
Vanillin,  624,  661,  664 
Synthesis  of,  662 
Vapor  density  by  Victor  Meyer  method, 

923 
van't  Hoff,  89,  243,  343 

-LeBel,  89,  176,  250,  305 
Vaseline,  43 
Vegetable  ivory,  380 
Verguin,  746 
Vicinal,  473 
Victor  Meyer  method  for  vapor  density, 

923 

Vieille,  378 
Vinegar,  135 
Vinyl  acetic  acid,  1  74 
Vinyl  alcohol,  166 
Vinyl  chloride,  164 
Vinyl  di-acetone  amine,  897 
Vinyl  halides,  164 
Viscose  silk,  374 
von  Humboldt,  43 
von  Schwann,  95 


Williams,  845 
Williamson,  105,  239 

synthesis,  105 

Willstatter,  891,  892,  893,  894 
Wislicenus,  176,  307 
Wohler,  i,  23,  429,  432 

synthesis,  432 
Wood  alcohol,  94 
Wood  distillation,  136 
Wood  pulp,  370 
Wood  spirits,  94 
Wurtz,  54,  105,  675 

reaction,  16,  24,  50,  106,  479,  730 

X 

Xanthic  acid,  368 
Xanthine,  448,  90x3,  903 

Imino,  449 

Synthesis  of,  901 
Xanthoproteic  reaction,  406 
Xylene,  476,  496,  498 

Meta,  482,  485 

Ortho,  482,  485 

Oxidation  of,  486 

Para,  482,  485 
Xylenes,  Isomeric,  476,  480 
Xylidine,  technical,  545 
Xylidines,  544 
Xylitol,  218 
Xyloic  acids,  687 
Xylose,  339 


Yeast,  95 


W 

Wagner,  500 

Water  type  compounds, 

Waxes,  144 

Weber,  846 

Wijs  solution,  214 


Zinc  alkyls,  76 

Zinc-ammonio  chloride,  612,  632,   779, 

783 

/iiu    mrthyl,  76 
Zinnin,  539 
Zymase,  96,  300 


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